GenomeRNAi - a database for RNAi phenotypes and reagents

Phenotype information for gene 1158 (CKM)

Screen TitleGene IDGene SymbolReagent IDScorePhenotypeFollow Up
Proliferation of cells with active beta-catenin (1)
CKM
 0,48
​		 none yes

Reference

CK1epsilon is required for breast cancers dependent on beta-catenin activity. Kim et al., 2010

Aberrant beta-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate beta-catenin activity for therapeutic purposes have proven elusive to date.

Screen Details

Stable ID: GR00221-A-1
Screen Title: Proliferation of cells with active beta-catenin (1)
Assay: Viability
Method: Luminescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: MCF7
Library: The RNAi Consortium (TRC), TRC shRNA Library
Reagent Type: shRNA
Score Type: B-score
Cutoff: < -1
Notes: Essential gene: gene with B-score < -1 for >= 2 shRNAs

Proliferation of cells with active beta-catenin (4)
CKM
 0,11
​		 none no

Reference

CK1epsilon is required for breast cancers dependent on beta-catenin activity. Kim et al., 2010

Aberrant beta-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate beta-catenin activity for therapeutic purposes have proven elusive to date.

Screen Details

Stable ID: GR00221-A-4
Screen Title: Proliferation of cells with active beta-catenin (4)
Assay: Viability
Method: Luminescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: T47D
Library: The RNAi Consortium (TRC), TRC shRNA Library
Reagent Type: shRNA
Score Type: B-score
Cutoff: < -1
Notes: Essential gene: gene with B-score < -1 for >= 2 shRNAs

Proliferation of cells with active beta-catenin (4)
CKM
 -0,06
​		 none no

Reference

CK1epsilon is required for breast cancers dependent on beta-catenin activity. Kim et al., 2010

Aberrant beta-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate beta-catenin activity for therapeutic purposes have proven elusive to date.

Screen Details

Stable ID: GR00221-A-4
Screen Title: Proliferation of cells with active beta-catenin (4)
Assay: Viability
Method: Luminescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: T47D
Library: The RNAi Consortium (TRC), TRC shRNA Library
Reagent Type: shRNA
Score Type: B-score
Cutoff: < -1
Notes: Essential gene: gene with B-score < -1 for >= 2 shRNAs

tau phosphorylation
CKM
CKM s1
 sp
​		 none no

Reference

High-content siRNA screening of the kinome identifies kinases involved in Alzheimer's disease-related tau hyperphosphorylation. Azorsa et al., 2010

Neurofibrillary tangles (NFT), a cardinal neuropathological feature of Alzheimer''s disease (AD) that is highly correlated with synaptic loss and dementia severity, appear to be partly attributable to increased phosphorylation of the microtubule stabilizing protein tau at certain AD-related residues. Identifying the kinases involved in the pathologic phosphorylation of tau may provide targets at which to aim new AD-modifying treatments.

Screen Details

Stable ID: GR00143-A
Screen Title: tau phosphorylation
Assay: Total tau and 12E8 tau protein expression
Method: Fluorescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: H4 overexpressing 4RON tau
Library: Qiagen, Validated human kinase siRNA Set 2.0
Reagent Type: siRNA
Score Type: p-value
Cutoff: Complex criteria
Notes:

Proliferation of cells with active beta-catenin (1)
CKM
 -0,65
​		 none yes

Reference

CK1epsilon is required for breast cancers dependent on beta-catenin activity. Kim et al., 2010

Aberrant beta-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate beta-catenin activity for therapeutic purposes have proven elusive to date.

Screen Details

Stable ID: GR00221-A-1
Screen Title: Proliferation of cells with active beta-catenin (1)
Assay: Viability
Method: Luminescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: MCF7
Library: The RNAi Consortium (TRC), TRC shRNA Library
Reagent Type: shRNA
Score Type: B-score
Cutoff: < -1
Notes: Essential gene: gene with B-score < -1 for >= 2 shRNAs

Proliferation of cells with active beta-catenin (4)
CKM
 1,16
​		 none no

Reference

CK1epsilon is required for breast cancers dependent on beta-catenin activity. Kim et al., 2010

Aberrant beta-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate beta-catenin activity for therapeutic purposes have proven elusive to date.

Screen Details

Stable ID: GR00221-A-4
Screen Title: Proliferation of cells with active beta-catenin (4)
Assay: Viability
Method: Luminescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: T47D
Library: The RNAi Consortium (TRC), TRC shRNA Library
Reagent Type: shRNA
Score Type: B-score
Cutoff: < -1
Notes: Essential gene: gene with B-score < -1 for >= 2 shRNAs

Ciliogenesis and cilium length (1)
1158
CKM
173
 25,71
​		 none no

Reference

Functional genomic screen for modulators of ciliogenesis and cilium length. Kim et al., 2010

Primary cilia are evolutionarily conserved cellular organelles that organize diverse signalling pathways. Defects in the formation or function of primary cilia are associated with a spectrum of human diseases and developmental abnormalities. Genetic screens in model organisms have discovered core machineries of cilium assembly and maintenance. However, regulatory molecules that coordinate the biogenesis of primary cilia with other cellular processes, including cytoskeletal organization, vesicle trafficking and cell-cell adhesion, remain to be identified. Here we report the results of a functional genomic screen using RNA interference (RNAi) to identify human genes involved in ciliogenesis control. The screen identified 36 positive and 13 negative ciliogenesis modulators, which include molecules involved in actin dynamics and vesicle trafficking. Further investigation demonstrated that blocking actin assembly facilitates ciliogenesis by stabilizing the pericentrosomal preciliary compartment (PPC), a previously uncharacterized compact vesiculotubular structure storing transmembrane proteins destined for cilia during the early phase of ciliogenesis. The PPC was labelled by recycling endosome markers. Moreover, knockdown of modulators that are involved in the endocytic recycling pathway affected the formation of the PPC as well as ciliogenesis. Our results uncover a critical regulatory step that couples actin dynamics and endocytic recycling with ciliogenesis, and also provides potential target molecules for future study.

Screen Details

Stable ID: GR00149-A-1
Screen Title: Ciliogenesis and cilium length (1)
Assay: Smoothed protein expression
Method: Fluorescence
Scope: Druggable genes
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: htRPE
Library: Ambion, Human druggable genome siRNA library V3.1
Reagent Type: siRNA
Score Type: Normalized percent inhibition
Cutoff: > 1.5 OR < -1.5 standard deviations from mean
Notes:

Proliferation of cells with active beta-catenin (1)
CKM
 1,08
​		 none yes

Reference

CK1epsilon is required for breast cancers dependent on beta-catenin activity. Kim et al., 2010

Aberrant beta-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate beta-catenin activity for therapeutic purposes have proven elusive to date.

Screen Details

Stable ID: GR00221-A-1
Screen Title: Proliferation of cells with active beta-catenin (1)
Assay: Viability
Method: Luminescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: MCF7
Library: The RNAi Consortium (TRC), TRC shRNA Library
Reagent Type: shRNA
Score Type: B-score
Cutoff: < -1
Notes: Essential gene: gene with B-score < -1 for >= 2 shRNAs

Proliferation of cells with active beta-catenin (3)
CKM
 0
​		 none yes

Reference

CK1epsilon is required for breast cancers dependent on beta-catenin activity. Kim et al., 2010

Aberrant beta-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate beta-catenin activity for therapeutic purposes have proven elusive to date.

Screen Details

Stable ID: GR00221-A-3
Screen Title: Proliferation of cells with active beta-catenin (3)
Assay: Viability
Method: Luminescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: MDA-MB-453
Library: The RNAi Consortium (TRC), TRC shRNA Library
Reagent Type: shRNA
Score Type: B-score
Cutoff: < -1
Notes: Essential gene: gene with B-score < -1 for >= 2 shRNAs

tau phosphorylation
CKM
CKM s2
 sp
​		 none no

Reference

High-content siRNA screening of the kinome identifies kinases involved in Alzheimer's disease-related tau hyperphosphorylation. Azorsa et al., 2010

Neurofibrillary tangles (NFT), a cardinal neuropathological feature of Alzheimer''s disease (AD) that is highly correlated with synaptic loss and dementia severity, appear to be partly attributable to increased phosphorylation of the microtubule stabilizing protein tau at certain AD-related residues. Identifying the kinases involved in the pathologic phosphorylation of tau may provide targets at which to aim new AD-modifying treatments.

Screen Details

Stable ID: GR00143-A
Screen Title: tau phosphorylation
Assay: Total tau and 12E8 tau protein expression
Method: Fluorescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: H4 overexpressing 4RON tau
Library: Qiagen, Validated human kinase siRNA Set 2.0
Reagent Type: siRNA
Score Type: p-value
Cutoff: Complex criteria
Notes:

Combinatorial effect with gemcitabine
CKM
CKM_A
 -0,17
​		 none no

Reference

Synthetic lethal RNAi screening identifies sensitizing targets for gemcitabine therapy in pancreatic cancer. Azorsa et al., 2009

Pancreatic cancer retains a poor prognosis among the gastrointestinal cancers. It affects 230,000 individuals worldwide, has a very high mortality rate, and remains one of the most challenging malignancies to treat successfully. Treatment with gemcitabine, the most widely used chemotherapeutic against pancreatic cancer, is not curative and resistance may occur. Combinations of gemcitabine with other chemotherapeutic drugs or biological agents have resulted in limited improvement.

Screen Details

Stable ID: GR00225-A
Screen Title: Combinatorial effect with gemcitabine
Assay: Viability (synthetic lethal)
Method: Luminescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: MIA PaCa-2
Library: Qiagen, Validated kinase siRNA library version 1.0
Reagent Type: siRNA
Score Type: log2 ratio
Cutoff: 1.65 SD below mean ratio level
Notes:

Aryl hydrocarbon receptor (AhR) transduction pathway regulation
1158
CKM
CKM_1
CKM_2
CKM_3
 np
​		 none no

Reference

RNAi-based screening identifies kinases interfering with dioxin-mediated up-regulation of CYP1A1 activity. Gilot et al., 2011

The aryl hydrocarbon receptor (AhR) is a transcription factor activated by several environmental pollutants, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and involved in carcinogenesis and various physiological processes, including immune response and endocrine functions. Characterization of kinases-related AhR transduction pathway remains an important purpose.

Screen Details

Stable ID: GR00155-A
Screen Title: Aryl hydrocarbon receptor (AhR) transduction pathway regulation
Assay: TCDD-induced CYP1A1-related EROD activity and cell viability
Method: Fluorescence and methylene blue
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: MCF-7
Library: Sigma-Genesys, MISSION siRNA Human Kinase Panel library
Reagent Type: siRNA
Score Type: Z-score
Cutoff: Top 150 for >= 2 of 3 siRNAs AND no effect on cell proliferation
Notes:

Proliferation of cells with active beta-catenin (3)
CKM
 0,32
​		 none yes

Reference

CK1epsilon is required for breast cancers dependent on beta-catenin activity. Kim et al., 2010

Aberrant beta-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate beta-catenin activity for therapeutic purposes have proven elusive to date.

Screen Details

Stable ID: GR00221-A-3
Screen Title: Proliferation of cells with active beta-catenin (3)
Assay: Viability
Method: Luminescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: MDA-MB-453
Library: The RNAi Consortium (TRC), TRC shRNA Library
Reagent Type: shRNA
Score Type: B-score
Cutoff: < -1
Notes: Essential gene: gene with B-score < -1 for >= 2 shRNAs

Combinatorial effect with gemcitabine
CKM
CKM_B
 -0,99
​		 none no

Reference

Synthetic lethal RNAi screening identifies sensitizing targets for gemcitabine therapy in pancreatic cancer. Azorsa et al., 2009

Pancreatic cancer retains a poor prognosis among the gastrointestinal cancers. It affects 230,000 individuals worldwide, has a very high mortality rate, and remains one of the most challenging malignancies to treat successfully. Treatment with gemcitabine, the most widely used chemotherapeutic against pancreatic cancer, is not curative and resistance may occur. Combinations of gemcitabine with other chemotherapeutic drugs or biological agents have resulted in limited improvement.

Screen Details

Stable ID: GR00225-A
Screen Title: Combinatorial effect with gemcitabine
Assay: Viability (synthetic lethal)
Method: Luminescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: MIA PaCa-2
Library: Qiagen, Validated kinase siRNA library version 1.0
Reagent Type: siRNA
Score Type: log2 ratio
Cutoff: 1.65 SD below mean ratio level
Notes:

Human papillomavirus oncogene expression regulation (1)
1158
CKM
 -1,39
​		 none no

Reference

Genome-wide siRNA screen identifies SMCX, EP400, and Brd4 as E2-dependent regulators of human papillomavirus oncogene expression. Smith et al., 2010

An essential step in the pathogenesis of human papillomavirus (HPV)-associated cancers is the dysregulated expression of the viral oncogenes. The papillomavirus E2 protein can silence the long control region (LCR) promoter that controls viral E6 and E7 oncogene expression. The mechanisms by which E2 represses oncogene expression and the cellular factors through which E2 mediates this silencing are largely unknown. We conducted an unbiased, genome-wide siRNA screen and series of secondary screens that identified 96 cellular genes that contribute to the repression of the HPV LCR. In addition to confirming a role for the E2-binding bromodomain protein Brd4 in E2-mediated silencing, we identified a number of genes that have not previously been implicated in E2 repression, including the demethylase JARID1C/SMCX as well as EP400, a component of the NuA4/TIP60 histone acetyltransferase complex. Each of these genes contributes independently and additively to E2-mediated silencing, indicating that E2 functions through several distinct cellular complexes to repress E6 and E7 expression.

Screen Details

Stable ID: GR00197-A-1
Screen Title: Human papillomavirus oncogene expression regulation (1)
Assay: HPV18 LCR reporter activity
Method: Luminescence
Scope: Genome-wide
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: C33A/BE2/18LCR c4
Library: Dharmacon, Human siGENOME SMARTpool library
Reagent Type: siRNA
Score Type: Z-score
Cutoff: >= 2
Notes: Author-submitted data; Phenotype strength according to Z-scores: weak: 2 - 3; moderate: 3 - 5; strong: > 5

Ciliogenesis and cilium length (1)
1158
CKM
173
 44,38
​		 none no

Reference

Functional genomic screen for modulators of ciliogenesis and cilium length. Kim et al., 2010

Primary cilia are evolutionarily conserved cellular organelles that organize diverse signalling pathways. Defects in the formation or function of primary cilia are associated with a spectrum of human diseases and developmental abnormalities. Genetic screens in model organisms have discovered core machineries of cilium assembly and maintenance. However, regulatory molecules that coordinate the biogenesis of primary cilia with other cellular processes, including cytoskeletal organization, vesicle trafficking and cell-cell adhesion, remain to be identified. Here we report the results of a functional genomic screen using RNA interference (RNAi) to identify human genes involved in ciliogenesis control. The screen identified 36 positive and 13 negative ciliogenesis modulators, which include molecules involved in actin dynamics and vesicle trafficking. Further investigation demonstrated that blocking actin assembly facilitates ciliogenesis by stabilizing the pericentrosomal preciliary compartment (PPC), a previously uncharacterized compact vesiculotubular structure storing transmembrane proteins destined for cilia during the early phase of ciliogenesis. The PPC was labelled by recycling endosome markers. Moreover, knockdown of modulators that are involved in the endocytic recycling pathway affected the formation of the PPC as well as ciliogenesis. Our results uncover a critical regulatory step that couples actin dynamics and endocytic recycling with ciliogenesis, and also provides potential target molecules for future study.

Screen Details

Stable ID: GR00149-A-1
Screen Title: Ciliogenesis and cilium length (1)
Assay: Smoothed protein expression
Method: Fluorescence
Scope: Druggable genes
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: htRPE
Library: Ambion, Human druggable genome siRNA library V3.1
Reagent Type: siRNA
Score Type: Normalized percent inhibition
Cutoff: > 1.5 OR < -1.5 standard deviations from mean
Notes:

Ciliogenesis and cilium length (1)
1158
CKM
172
 75,42
​		 none no

Reference

Functional genomic screen for modulators of ciliogenesis and cilium length. Kim et al., 2010

Primary cilia are evolutionarily conserved cellular organelles that organize diverse signalling pathways. Defects in the formation or function of primary cilia are associated with a spectrum of human diseases and developmental abnormalities. Genetic screens in model organisms have discovered core machineries of cilium assembly and maintenance. However, regulatory molecules that coordinate the biogenesis of primary cilia with other cellular processes, including cytoskeletal organization, vesicle trafficking and cell-cell adhesion, remain to be identified. Here we report the results of a functional genomic screen using RNA interference (RNAi) to identify human genes involved in ciliogenesis control. The screen identified 36 positive and 13 negative ciliogenesis modulators, which include molecules involved in actin dynamics and vesicle trafficking. Further investigation demonstrated that blocking actin assembly facilitates ciliogenesis by stabilizing the pericentrosomal preciliary compartment (PPC), a previously uncharacterized compact vesiculotubular structure storing transmembrane proteins destined for cilia during the early phase of ciliogenesis. The PPC was labelled by recycling endosome markers. Moreover, knockdown of modulators that are involved in the endocytic recycling pathway affected the formation of the PPC as well as ciliogenesis. Our results uncover a critical regulatory step that couples actin dynamics and endocytic recycling with ciliogenesis, and also provides potential target molecules for future study.

Screen Details

Stable ID: GR00149-A-1
Screen Title: Ciliogenesis and cilium length (1)
Assay: Smoothed protein expression
Method: Fluorescence
Scope: Druggable genes
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: htRPE
Library: Ambion, Human druggable genome siRNA library V3.1
Reagent Type: siRNA
Score Type: Normalized percent inhibition
Cutoff: > 1.5 OR < -1.5 standard deviations from mean
Notes:

Proliferation of cells with active beta-catenin (2)
CKM
 1,36
​		 none yes

Reference

CK1epsilon is required for breast cancers dependent on beta-catenin activity. Kim et al., 2010

Aberrant beta-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate beta-catenin activity for therapeutic purposes have proven elusive to date.

Screen Details

Stable ID: GR00221-A-2
Screen Title: Proliferation of cells with active beta-catenin (2)
Assay: Viability
Method: Luminescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: MDA-MB-231
Library: The RNAi Consortium (TRC), TRC shRNA Library
Reagent Type: shRNA
Score Type: B-score
Cutoff: < -1
Notes: Essential gene: gene with B-score < -1 for >= 2 shRNAs

Proliferation of cells with active beta-catenin (3)
CKM
 0,75
​		 none yes

Reference

CK1epsilon is required for breast cancers dependent on beta-catenin activity. Kim et al., 2010

Aberrant beta-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate beta-catenin activity for therapeutic purposes have proven elusive to date.

Screen Details

Stable ID: GR00221-A-3
Screen Title: Proliferation of cells with active beta-catenin (3)
Assay: Viability
Method: Luminescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: MDA-MB-453
Library: The RNAi Consortium (TRC), TRC shRNA Library
Reagent Type: shRNA
Score Type: B-score
Cutoff: < -1
Notes: Essential gene: gene with B-score < -1 for >= 2 shRNAs

Combinatorial effect with gemcitabine
CKM
CKM_A
 -0,96
​		 none no

Reference

Synthetic lethal RNAi screening identifies sensitizing targets for gemcitabine therapy in pancreatic cancer. Azorsa et al., 2009

Pancreatic cancer retains a poor prognosis among the gastrointestinal cancers. It affects 230,000 individuals worldwide, has a very high mortality rate, and remains one of the most challenging malignancies to treat successfully. Treatment with gemcitabine, the most widely used chemotherapeutic against pancreatic cancer, is not curative and resistance may occur. Combinations of gemcitabine with other chemotherapeutic drugs or biological agents have resulted in limited improvement.

Screen Details

Stable ID: GR00225-A
Screen Title: Combinatorial effect with gemcitabine
Assay: Viability (synthetic lethal)
Method: Luminescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: MIA PaCa-2
Library: Qiagen, Validated kinase siRNA library version 1.0
Reagent Type: siRNA
Score Type: log2 ratio
Cutoff: 1.65 SD below mean ratio level
Notes:

Proliferation of cells with active beta-catenin (1)
CKM
 0,46
​		 none yes

Reference

CK1epsilon is required for breast cancers dependent on beta-catenin activity. Kim et al., 2010

Aberrant beta-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate beta-catenin activity for therapeutic purposes have proven elusive to date.

Screen Details

Stable ID: GR00221-A-1
Screen Title: Proliferation of cells with active beta-catenin (1)
Assay: Viability
Method: Luminescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: MCF7
Library: The RNAi Consortium (TRC), TRC shRNA Library
Reagent Type: shRNA
Score Type: B-score
Cutoff: < -1
Notes: Essential gene: gene with B-score < -1 for >= 2 shRNAs

Proliferation of cells with active beta-catenin (4)
CKM
 -0,52
​		 none no

Reference

CK1epsilon is required for breast cancers dependent on beta-catenin activity. Kim et al., 2010

Aberrant beta-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate beta-catenin activity for therapeutic purposes have proven elusive to date.

Screen Details

Stable ID: GR00221-A-4
Screen Title: Proliferation of cells with active beta-catenin (4)
Assay: Viability
Method: Luminescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: T47D
Library: The RNAi Consortium (TRC), TRC shRNA Library
Reagent Type: shRNA
Score Type: B-score
Cutoff: < -1
Notes: Essential gene: gene with B-score < -1 for >= 2 shRNAs

Ciliogenesis and cilium length (1)
1158
CKM
146037
 1,85
​		 none no

Reference

Functional genomic screen for modulators of ciliogenesis and cilium length. Kim et al., 2010

Primary cilia are evolutionarily conserved cellular organelles that organize diverse signalling pathways. Defects in the formation or function of primary cilia are associated with a spectrum of human diseases and developmental abnormalities. Genetic screens in model organisms have discovered core machineries of cilium assembly and maintenance. However, regulatory molecules that coordinate the biogenesis of primary cilia with other cellular processes, including cytoskeletal organization, vesicle trafficking and cell-cell adhesion, remain to be identified. Here we report the results of a functional genomic screen using RNA interference (RNAi) to identify human genes involved in ciliogenesis control. The screen identified 36 positive and 13 negative ciliogenesis modulators, which include molecules involved in actin dynamics and vesicle trafficking. Further investigation demonstrated that blocking actin assembly facilitates ciliogenesis by stabilizing the pericentrosomal preciliary compartment (PPC), a previously uncharacterized compact vesiculotubular structure storing transmembrane proteins destined for cilia during the early phase of ciliogenesis. The PPC was labelled by recycling endosome markers. Moreover, knockdown of modulators that are involved in the endocytic recycling pathway affected the formation of the PPC as well as ciliogenesis. Our results uncover a critical regulatory step that couples actin dynamics and endocytic recycling with ciliogenesis, and also provides potential target molecules for future study.

Screen Details

Stable ID: GR00149-A-1
Screen Title: Ciliogenesis and cilium length (1)
Assay: Smoothed protein expression
Method: Fluorescence
Scope: Druggable genes
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: htRPE
Library: Ambion, Human druggable genome siRNA library V3.1
Reagent Type: siRNA
Score Type: Normalized percent inhibition
Cutoff: > 1.5 OR < -1.5 standard deviations from mean
Notes:

Proliferation of cells with active beta-catenin (2)
CKM
 0,58
​		 none yes

Reference

CK1epsilon is required for breast cancers dependent on beta-catenin activity. Kim et al., 2010

Aberrant beta-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate beta-catenin activity for therapeutic purposes have proven elusive to date.

Screen Details

Stable ID: GR00221-A-2
Screen Title: Proliferation of cells with active beta-catenin (2)
Assay: Viability
Method: Luminescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: MDA-MB-231
Library: The RNAi Consortium (TRC), TRC shRNA Library
Reagent Type: shRNA
Score Type: B-score
Cutoff: < -1
Notes: Essential gene: gene with B-score < -1 for >= 2 shRNAs

Cell division (1)
ENSG00000104879
CKM
ENSG00000104879
 sp
​		 none no

Reference

Genome-scale RNAi profiling of cell division in human tissue culture cells. Kittler et al., 2007

Cell division is fundamental for all organisms. Here we report a genome-scale RNA-mediated interference screen in HeLa cells designed to identify human genes that are important for cell division. We have used a library of endoribonuclease-prepared short interfering RNAs for gene silencing and have used DNA content analysis to identify genes that induced cell cycle arrest or altered ploidy on silencing. Validation and secondary assays were performed to generate a nine-parameter loss-of-function phenoprint for each of the genes. These phenotypic signatures allowed the assignment of genes to specific functional classes by combining hierarchical clustering, cross-species analysis and proteomic data mining. We highlight the richness of our dataset by ascribing novel functions to genes in mitosis and cytokinesis. In particular, we identify two evolutionarily conserved transcriptional regulatory networks that govern cytokinesis. Our work provides an experimental framework from which the systematic analysis of novel genes necessary for cell division in human cells can begin.

Screen Details

Stable ID: GR00098-A-1
Screen Title: Cell division (1)
Assay: Cell number and DNA content
Method: Laser scanning cytometry
Scope: Genome-wide
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: HeLa
Library: Custom-made, rp
Reagent Type: esiRNA
Score Type: Complex, sp
Cutoff: Complex criteria
Notes:

Proliferation of cells with active beta-catenin (2)
CKM
 -2,59
​		 Decreased viability yes

Reference

CK1epsilon is required for breast cancers dependent on beta-catenin activity. Kim et al., 2010

Aberrant beta-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate beta-catenin activity for therapeutic purposes have proven elusive to date.

Screen Details

Stable ID: GR00221-A-2
Screen Title: Proliferation of cells with active beta-catenin (2)
Assay: Viability
Method: Luminescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: MDA-MB-231
Library: The RNAi Consortium (TRC), TRC shRNA Library
Reagent Type: shRNA
Score Type: B-score
Cutoff: < -1
Notes: Essential gene: gene with B-score < -1 for >= 2 shRNAs

Homologous recombination DNA double-strand break repair (HR-DSBR) (1)
ENSG00000104879
CKM
np
 -0,3
​		 none no

Reference

A genome-scale DNA repair RNAi screen identifies SPG48 as a novel gene associated with hereditary spastic paraplegia. Słabicki et al., 2010

DNA repair is essential to maintain genome integrity, and genes with roles in DNA repair are frequently mutated in a variety of human diseases. Repair via homologous recombination typically restores the original DNA sequence without introducing mutations, and a number of genes that are required for homologous recombination DNA double-strand break repair (HR-DSBR) have been identified. However, a systematic analysis of this important DNA repair pathway in mammalian cells has not been reported. Here, we describe a genome-scale endoribonuclease-prepared short interfering RNA (esiRNA) screen for genes involved in DNA double strand break repair. We report 61 genes that influenced the frequency of HR-DSBR and characterize in detail one of the genes that decreased the frequency of HR-DSBR. We show that the gene KIAA0415 encodes a putative helicase that interacts with SPG11 and SPG15, two proteins mutated in hereditary spastic paraplegia (HSP). We identify mutations in HSP patients, discovering KIAA0415/SPG48 as a novel HSP-associated gene, and show that a KIAA0415/SPG48 mutant cell line is more sensitive to DNA damaging drugs. We present the first genome-scale survey of HR-DSBR in mammalian cells providing a dataset that should accelerate the discovery of novel genes with roles in DNA repair and associated medical conditions. The discovery that proteins forming a novel protein complex are required for efficient HR-DSBR and are mutated in patients suffering from HSP suggests a link between HSP and DNA repair.

Screen Details

Stable ID: GR00151-A-1
Screen Title: Homologous recombination DNA double-strand break repair (HR-DSBR) (1)
Assay: (HR-DSBR) DR-GFP reporter
Method: Flow cytometry
Scope: Genome-wide
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: HeLa
Library: Custom-made, Custom-made
Reagent Type: esiRNA
Score Type: Z-score
Cutoff: < -2 OR > 2
Notes:

Self-renewal and pluripotency in human embryonic stem cells (1)
NM_001824
CKM
 -0,56
​		 none no

Reference

A genome-wide RNAi screen reveals determinants of human embryonic stem cell identity. Chia et al., 2010

The derivation of human ES cells (hESCs) from human blastocysts represents one of the milestones in stem cell biology. The full potential of hESCs in research and clinical applications requires a detailed understanding of the genetic network that governs the unique properties of hESCs. Here, we report a genome-wide RNA interference screen to identify genes which regulate self-renewal and pluripotency properties in hESCs. Interestingly, functionally distinct complexes involved in transcriptional regulation and chromatin remodelling are among the factors identified in the screen. To understand the roles of these potential regulators of hESCs, we studied transcription factor PRDM14 to gain new insights into its functional roles in the regulation of pluripotency. We showed that PRDM14 regulates directly the expression of key pluripotency gene POU5F1 through its proximal enhancer. Genome-wide location profiling experiments revealed that PRDM14 colocalized extensively with other key transcription factors such as OCT4, NANOG and SOX2, indicating that PRDM14 is integrated into the core transcriptional regulatory network. More importantly, in a gain-of-function assay, we showed that PRDM14 is able to enhance the efficiency of reprogramming of human fibroblasts in conjunction with OCT4, SOX2 and KLF4. Altogether, our study uncovers a wealth of novel hESC regulators wherein PRDM14 exemplifies a key transcription factor required for the maintenance of hESC identity and the reacquisition of pluripotency in human somatic cells.

Screen Details

Stable ID: GR00184-A-1
Screen Title: Self-renewal and pluripotency in human embryonic stem cells (1)
Assay: POU5F1 protein expression
Method: Fluorescence
Scope: Genome-wide
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: hESC H1
Library: Dharmacon, SMARTpool siRNA library
Reagent Type: siRNA
Score Type: Z-score
Cutoff: < -2
Notes:

Genome stability
NM_001824
CKM
np
 sp
​		 none no

Reference

A genome-wide siRNA screen reveals diverse cellular processes and pathways that mediate genome stability. Paulsen et al., 2009

Signaling pathways that respond to DNA damage are essential for the maintenance of genome stability and are linked to many diseases, including cancer. Here, a genome-wide siRNA screen was employed to identify additional genes involved in genome stabilization by monitoring phosphorylation of the histone variant H2AX, an early mark of DNA damage. We identified hundreds of genes whose downregulation led to elevated levels of H2AX phosphorylation (gammaH2AX) and revealed links to cellular complexes and to genes with unclassified functions. We demonstrate a widespread role for mRNA-processing factors in preventing DNA damage, which in some cases is caused by aberrant RNA-DNA structures. Furthermore, we connect increased gammaH2AX levels to the neurological disorder Charcot-Marie-Tooth (CMT) syndrome, and we find a role for several CMT proteins in the DNA-damage response. These data indicate that preservation of genome stability is mediated by a larger network of biological processes than previously appreciated.

Screen Details

Stable ID: GR00053-A
Screen Title: Genome stability
Assay: gamma-H2AX phosphorylation and DNA content
Method: Fluorescence
Scope: Genome-wide
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: HeLa
Library: ThermoFisher Scientific, siARRAY human genome siRNA library
Reagent Type: siRNA
Score Type: p-value
Cutoff: Complex criteria
Notes: Confidence groupings from 4 to 1 (highest level of confidence in group 4)

Combinatorial effect with gemcitabine
CKM
CKM_B
 -0,28
​		 none no

Reference

Synthetic lethal RNAi screening identifies sensitizing targets for gemcitabine therapy in pancreatic cancer. Azorsa et al., 2009

Pancreatic cancer retains a poor prognosis among the gastrointestinal cancers. It affects 230,000 individuals worldwide, has a very high mortality rate, and remains one of the most challenging malignancies to treat successfully. Treatment with gemcitabine, the most widely used chemotherapeutic against pancreatic cancer, is not curative and resistance may occur. Combinations of gemcitabine with other chemotherapeutic drugs or biological agents have resulted in limited improvement.

Screen Details

Stable ID: GR00225-A
Screen Title: Combinatorial effect with gemcitabine
Assay: Viability (synthetic lethal)
Method: Luminescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: MIA PaCa-2
Library: Qiagen, Validated kinase siRNA library version 1.0
Reagent Type: siRNA
Score Type: log2 ratio
Cutoff: 1.65 SD below mean ratio level
Notes:

Ciliogenesis and cilium length (1)
1158
CKM
172
 88,05
​		 none no

Reference

Functional genomic screen for modulators of ciliogenesis and cilium length. Kim et al., 2010

Primary cilia are evolutionarily conserved cellular organelles that organize diverse signalling pathways. Defects in the formation or function of primary cilia are associated with a spectrum of human diseases and developmental abnormalities. Genetic screens in model organisms have discovered core machineries of cilium assembly and maintenance. However, regulatory molecules that coordinate the biogenesis of primary cilia with other cellular processes, including cytoskeletal organization, vesicle trafficking and cell-cell adhesion, remain to be identified. Here we report the results of a functional genomic screen using RNA interference (RNAi) to identify human genes involved in ciliogenesis control. The screen identified 36 positive and 13 negative ciliogenesis modulators, which include molecules involved in actin dynamics and vesicle trafficking. Further investigation demonstrated that blocking actin assembly facilitates ciliogenesis by stabilizing the pericentrosomal preciliary compartment (PPC), a previously uncharacterized compact vesiculotubular structure storing transmembrane proteins destined for cilia during the early phase of ciliogenesis. The PPC was labelled by recycling endosome markers. Moreover, knockdown of modulators that are involved in the endocytic recycling pathway affected the formation of the PPC as well as ciliogenesis. Our results uncover a critical regulatory step that couples actin dynamics and endocytic recycling with ciliogenesis, and also provides potential target molecules for future study.

Screen Details

Stable ID: GR00149-A-1
Screen Title: Ciliogenesis and cilium length (1)
Assay: Smoothed protein expression
Method: Fluorescence
Scope: Druggable genes
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: htRPE
Library: Ambion, Human druggable genome siRNA library V3.1
Reagent Type: siRNA
Score Type: Normalized percent inhibition
Cutoff: > 1.5 OR < -1.5 standard deviations from mean
Notes:

Proliferation of cells with active beta-catenin (2)
CKM
 -1,35
​		 Decreased viability yes

Reference

CK1epsilon is required for breast cancers dependent on beta-catenin activity. Kim et al., 2010

Aberrant beta-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate beta-catenin activity for therapeutic purposes have proven elusive to date.

Screen Details

Stable ID: GR00221-A-2
Screen Title: Proliferation of cells with active beta-catenin (2)
Assay: Viability
Method: Luminescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: MDA-MB-231
Library: The RNAi Consortium (TRC), TRC shRNA Library
Reagent Type: shRNA
Score Type: B-score
Cutoff: < -1
Notes: Essential gene: gene with B-score < -1 for >= 2 shRNAs

Salmonella enterica subspecies 1 serovar Typhimurium invasion (1)
1158
CKM
np
 -0,04
​		 none no

Reference

RNAi screen of Salmonella invasion shows role of COPI in membrane targeting of cholesterol and Cdc42. Misselwitz et al., 2011

The pathogen Salmonella Typhimurium is a common cause of diarrhea and invades the gut tissue by injecting a cocktail of virulence factors into epithelial cells, triggering actin rearrangements, membrane ruffling and pathogen entry. One of these factors is SopE, a G-nucleotide exchange factor for the host cellular Rho GTPases Rac1 and Cdc42. How SopE mediates cellular invasion is incompletely understood. Using genome-scale RNAi screening we identified 72 known and novel host cell proteins affecting SopE-mediated entry. Follow-up assays assigned these ''hits'' to particular steps of the invasion process; i.e., binding, effector injection, membrane ruffling, membrane closure and maturation of the Salmonella-containing vacuole. Depletion of the COPI complex revealed a unique effect on virulence factor injection and membrane ruffling. Both effects are attributable to mislocalization of cholesterol, sphingolipids, Rac1 and Cdc42 away from the plasma membrane into a large intracellular compartment. Equivalent results were obtained with the vesicular stomatitis virus. Therefore, COPI-facilitated maintenance of lipids may represent a novel, unifying mechanism essential for a wide range of pathogens, offering opportunities for designing new drugs.

Screen Details

Stable ID: GR00133-A-1
Screen Title: Salmonella enterica subspecies 1 serovar Typhimurium invasion (1)
Assay: Gentamycin protection invasion assay
Method: Fluorescence
Scope: Druggable genes
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: HeLa
Library: Qiagen, Druggable genome library V2.0
Reagent Type: siRNA
Score Type: log2 median
Cutoff: Complex criteria
Notes:

Melanogenesis
NM_001824
CKM
np
 0,97
​		 none no

Reference

Genome-wide siRNA-based functional genomics of pigmentation identifies novel genes and pathways that impact melanogenesis in human cells. Ganesan et al., 2008

Melanin protects the skin and eyes from the harmful effects of UV irradiation, protects neural cells from toxic insults, and is required for sound conduction in the inner ear. Aberrant regulation of melanogenesis underlies skin disorders (melasma and vitiligo), neurologic disorders (Parkinson''s disease), auditory disorders (Waardenburg''s syndrome), and opthalmologic disorders (age related macular degeneration). Much of the core synthetic machinery driving melanin production has been identified; however, the spectrum of gene products participating in melanogenesis in different physiological niches is poorly understood. Functional genomics based on RNA-mediated interference (RNAi) provides the opportunity to derive unbiased comprehensive collections of pharmaceutically tractable single gene targets supporting melanin production. In this study, we have combined a high-throughput, cell-based, one-well/one-gene screening platform with a genome-wide arrayed synthetic library of chemically synthesized, small interfering RNAs to identify novel biological pathways that govern melanin biogenesis in human melanocytes. Ninety-two novel genes that support pigment production were identified with a low false discovery rate. Secondary validation and preliminary mechanistic studies identified a large panel of targets that converge on tyrosinase expression and stability. Small molecule inhibition of a family of gene products in this class was sufficient to impair chronic tyrosinase expression in pigmented melanoma cells and UV-induced tyrosinase expression in primary melanocytes. Isolation of molecular machinery known to support autophagosome biosynthesis from this screen, together with in vitro and in vivo validation, exposed a close functional relationship between melanogenesis and autophagy. In summary, these studies illustrate the power of RNAi-based functional genomics to identify novel genes, pathways, and pharmacologic agents that impact a biological phenotype and operate outside of preconceived mechanistic relationships.

Screen Details

Stable ID: GR00056-A
Screen Title: Melanogenesis
Assay: Melanin protein expression and viability
Method: Absorbance and luminescence
Scope: Genome-wide
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: MNT-1
Library: Dharmacon, rp
Reagent Type: siRNA
Score Type: Normalized absorbance ratio
Cutoff: > 2 standard deviations below mean
Notes: Additional information about a secondary screen (retest to determine false-positive rate)

Combinatorial effect with paclitaxel
NM_001824
CKM
np
 1,1
​		 none no

Reference

Synthetic lethal screen identification of chemosensitizer loci in cancer cells. Whitehurst et al., 2007

Abundant evidence suggests that a unifying principle governing the molecular pathology of cancer is the co-dependent aberrant regulation of core machinery driving proliferation and suppressing apoptosis. Anomalous proteins engaged in support of this tumorigenic regulatory environment most probably represent optimal intervention targets in a heterogeneous population of cancer cells. The advent of RNA-mediated interference (RNAi)-based functional genomics provides the opportunity to derive unbiased comprehensive collections of validated gene targets supporting critical biological systems outside the framework of preconceived notions of mechanistic relationships. We have combined a high-throughput cell-based one-well/one-gene screening platform with a genome-wide synthetic library of chemically synthesized small interfering RNAs for systematic interrogation of the molecular underpinnings of cancer cell chemoresponsiveness. NCI-H1155, a human non-small-cell lung cancer line, was employed in a paclitaxel-dependent synthetic lethal screen designed to identify gene targets that specifically reduce cell viability in the presence of otherwise sublethal concentrations of paclitaxel. Using a stringent objective statistical algorithm to reduce false discovery rates below 5%, we isolated a panel of 87 genes that represent major focal points of the autonomous response of cancer cells to the abrogation of microtubule dynamics. Here we show that several of these targets sensitize lung cancer cells to paclitaxel concentrations 1,000-fold lower than otherwise required for a significant response, and we identify mechanistic relationships between cancer-associated aberrant gene expression programmes and the basic cellular machinery required for robust mitotic progression.

Screen Details

Stable ID: GR00054-A
Screen Title: Combinatorial effect with paclitaxel
Assay: Viability (synthetic lethal)
Method: ATP level
Scope: Genome-wide
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: NCI-H1155
Library: Dharmacon, # G-005000-01
Reagent Type: siRNA
Score Type: Paclitaxel/control ratio
Cutoff: Complex criteria
Notes: Additional information about 87 high-confidence hits

Borna disease virus infection
1158
CKM
CKM siRNA2
CKM siRNA3
CKM siRNA1
 sp
​		 Increased viability after borna disease (rVSVΔG*/BDVG) virus infection yes

Reference

Identification of host factors involved in borna disease virus cell entry through a small interfering RNA functional genetic screen. Clemente et al., 2010

Borna disease virus (BDV), the prototypic member of the Bornaviridae family, within the order Mononegavirales, is highly neurotropic and constitutes an important model system for the study of viral persistence in the central nervous system (CNS) and associated disorders. The virus surface glycoprotein (G) has been shown to direct BDV cell entry via receptor-mediated endocytosis, but the mechanisms governing cell tropism and propagation of BDV within the CNS are unknown. We developed a small interfering RNA (siRNA)-based screening to identify cellular genes and pathways that specifically contribute to BDV G-mediated cell entry. Our screen relied on silencing-mediated increased survival of cells infected with rVSVDeltaG*/BDVG, a cytolytic recombinant vesicular stomatitis virus expressing BDV G that mimics the cell tropism and entry pathway of bona fide BDV. We identified 24 cellular genes involved in BDV G-mediated cell entry. Identified genes are known to participate in a broad range of distinct cellular functions, revealing a complex process associated with BDV cell entry. The siRNA-based screening strategy we have developed should be applicable to identify cellular genes contributing to cell entry mediated by surface G proteins of other viruses.

Screen Details

Stable ID: GR00192-A
Screen Title: Borna disease virus infection
Assay: Viability
Method: Luminescence
Scope: Druggable genes
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: Ol
Library: Ambion, Silencer Human Druggable Genome siRNA Library V2
Reagent Type: siRNA
Score Type: Fold change
Cutoff: >= 2 for at least 2 siRNAs
Notes: Additional information about secondary screens (rVSVΔG*/VSVG infection, etc.)

Proliferation of cells with active beta-catenin (3)
CKM
 2,27
​		 none yes

Reference

CK1epsilon is required for breast cancers dependent on beta-catenin activity. Kim et al., 2010

Aberrant beta-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate beta-catenin activity for therapeutic purposes have proven elusive to date.

Screen Details

Stable ID: GR00221-A-3
Screen Title: Proliferation of cells with active beta-catenin (3)
Assay: Viability
Method: Luminescence
Scope: Kinases
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: MDA-MB-453
Library: The RNAi Consortium (TRC), TRC shRNA Library
Reagent Type: shRNA
Score Type: B-score
Cutoff: < -1
Notes: Essential gene: gene with B-score < -1 for >= 2 shRNAs

Hepatitis C virus replication (1)
1158
CKM
PL-50001
 0,87
​		 none no

Reference

A functional genomic screen identifies cellular cofactors of hepatitis C virus replication. Tai et al., 2009

Hepatitis C virus (HCV) chronically infects 3% of the world''s population, and complications from HCV are the leading indication for liver transplantation. Given the need for better anti-HCV therapies, one strategy is to identify and target cellular cofactors of the virus lifecycle. Using a genome-wide siRNA library, we identified 96 human genes that support HCV replication, with a significant number of them being involved in vesicle organization and biogenesis. Phosphatidylinositol 4-kinase PI4KA and multiple subunits of the COPI vesicle coat complex were among the genes identified. Consistent with this, pharmacologic inhibitors of COPI and PI4KA blocked HCV replication. Targeting hepcidin, a peptide critical for iron homeostasis, also affected HCV replication, which may explain the known dysregulation of iron homeostasis in HCV infection. The host cofactors for HCV replication identified in this study should serve as a useful resource in delineating new targets for anti-HCV therapies.

Screen Details

Stable ID: GR00180-A-1
Screen Title: Hepatitis C virus replication (1)
Assay: HCV replicon RNA copy number
Method: Luminescence
Scope: Genome-wide
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: Huh7/Rep-Feo
Library: Dharmacon, siARRAY Human Genome siRNA Library
Reagent Type: siRNA
Score Type: q-value
Cutoff: Complex criteria
Notes:

Ciliogenesis and cilium length (1)
1158
CKM
146037
 4,78
​		 none no

Reference

Functional genomic screen for modulators of ciliogenesis and cilium length. Kim et al., 2010

Primary cilia are evolutionarily conserved cellular organelles that organize diverse signalling pathways. Defects in the formation or function of primary cilia are associated with a spectrum of human diseases and developmental abnormalities. Genetic screens in model organisms have discovered core machineries of cilium assembly and maintenance. However, regulatory molecules that coordinate the biogenesis of primary cilia with other cellular processes, including cytoskeletal organization, vesicle trafficking and cell-cell adhesion, remain to be identified. Here we report the results of a functional genomic screen using RNA interference (RNAi) to identify human genes involved in ciliogenesis control. The screen identified 36 positive and 13 negative ciliogenesis modulators, which include molecules involved in actin dynamics and vesicle trafficking. Further investigation demonstrated that blocking actin assembly facilitates ciliogenesis by stabilizing the pericentrosomal preciliary compartment (PPC), a previously uncharacterized compact vesiculotubular structure storing transmembrane proteins destined for cilia during the early phase of ciliogenesis. The PPC was labelled by recycling endosome markers. Moreover, knockdown of modulators that are involved in the endocytic recycling pathway affected the formation of the PPC as well as ciliogenesis. Our results uncover a critical regulatory step that couples actin dynamics and endocytic recycling with ciliogenesis, and also provides potential target molecules for future study.

Screen Details

Stable ID: GR00149-A-1
Screen Title: Ciliogenesis and cilium length (1)
Assay: Smoothed protein expression
Method: Fluorescence
Scope: Druggable genes
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: htRPE
Library: Ambion, Human druggable genome siRNA library V3.1
Reagent Type: siRNA
Score Type: Normalized percent inhibition
Cutoff: > 1.5 OR < -1.5 standard deviations from mean
Notes:

TP53 interactions (1)
ENSG00000104879
np
 sp
​		 none no

Reference

A systematic RNAi synthetic interaction screen reveals a link between p53 and snoRNP assembly. Krastev et al., 2011

TP53 (tumour protein 53) is one of the most frequently mutated genes in human cancer and its role during cellular transformation has been studied extensively. However, the homeostatic functions of p53 are less well understood. Here, we explore the molecular dependency network of TP53 through an RNAi-mediated synthetic interaction screen employing two HCT116 isogenic cell lines and a genome-scale endoribonuclease-prepared short interfering RNA library. We identify a variety of TP53 synthetic interactions unmasking the complex connections of p53 to cellular physiology and growth control. Molecular dissection of the TP53 synthetic interaction with UNRIP indicates an enhanced dependency of TP53-negative cells on small nucleolar ribonucleoprotein (snoRNP) assembly. This dependency is mediated by the snoRNP chaperone gene NOLC1 (also known as NOPP140), which we identify as a physiological p53 target gene. This unanticipated function of TP53 in snoRNP assembly highlights the potential of RNAi-mediated synthetic interaction screens to dissect molecular pathways of tumour suppressor genes.

Screen Details

Stable ID: GR00196-A-1
Screen Title: TP53 interactions (1)
Assay: TP53 protein expression and viability
Method: Fluorescence
Scope: Genome-wide
Screen Type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: HCT116 ( wildtype and TP53 knockout)
Library: Custom-made, rp
Reagent Type: esiRNA
Score Type: Complex, sp
Cutoff: Complex criteria
Notes:

Reagent information for gene 1158 (CKM)

Reagent IDTypeLibrary
TRCN0000197275 shRNA
TRC shRNA Library|The RNAi Consortium (TRC)|1|RefSeq|81054|shRNA|http://www.broadinstitute.org/rnai/public/
TRCN0000195432 shRNA
TRC shRNA Library|The RNAi Consortium (TRC)|1|RefSeq|81054|shRNA|http://www.broadinstitute.org/rnai/public/
TRCN0000010089 shRNA
TRC shRNA Library|The RNAi Consortium (TRC)|1|RefSeq|81054|shRNA|http://www.broadinstitute.org/rnai/public/
TRCN0000010090 shRNA
TRC shRNA Library|The RNAi Consortium (TRC)|1|RefSeq|81054|shRNA|http://www.broadinstitute.org/rnai/public/
TRCN0000010088 shRNA
TRC shRNA Library|The RNAi Consortium (TRC)|1|RefSeq|81054|shRNA|http://www.broadinstitute.org/rnai/public/
TRCN0000199607 shRNA
TRC shRNA Library|The RNAi Consortium (TRC)|1|RefSeq|81054|shRNA|http://www.broadinstitute.org/rnai/public/
TRCN0000199651 shRNA
TRC shRNA Library|The RNAi Consortium (TRC)|1|RefSeq|81054|shRNA|http://www.broadinstitute.org/rnai/public/
TRCN0000010091 shRNA
TRC shRNA Library|The RNAi Consortium (TRC)|1|RefSeq|81054|shRNA|http://www.broadinstitute.org/rnai/public/
D-006707-01 siRNA
siGENOME|Thermo Scientific Dharmacon|1|RefSeq release 5-7|84206 siRNAs in pools of four|siRNA|http://www.dharmacon.com/
D-006707-02 siRNA
siGENOME|Thermo Scientific Dharmacon|1|RefSeq release 5-7|84206 siRNAs in pools of four|siRNA|http://www.dharmacon.com/
D-006707-03 siRNA
siGENOME|Thermo Scientific Dharmacon|1|RefSeq release 5-7|84206 siRNAs in pools of four|siRNA|http://www.dharmacon.com/
D-006707-04 siRNA
siGENOME|Thermo Scientific Dharmacon|1|RefSeq release 5-7|84206 siRNAs in pools of four|siRNA|http://www.dharmacon.com/
SI00028770 siRNA
Druggable and whole genome supplement|Qiagen|1, 3|RefSeq|70308 siRNAs in pools of four|siRNA|http://www.qiagen.com/
SI00028777 siRNA
Druggable and whole genome supplement|Qiagen|1, 3|RefSeq|70308 siRNAs in pools of four|siRNA|http://www.qiagen.com/
SI00028763 siRNA
Druggable and whole genome supplement|Qiagen|1, 3|RefSeq|70308 siRNAs in pools of four|siRNA|http://www.qiagen.com/
SI02665285 siRNA
Druggable and whole genome supplement|Qiagen|1, 3|RefSeq|70308 siRNAs in pools of four|siRNA|http://www.qiagen.com/
s3094 siRNA
Ambion Silencer Select|Ambion|1|RefSeq|64781|siRNA|http://www.invitrogen.com/site/us/en/home/brands/ambion.html?CID=fl-ambion
s3095 siRNA
Ambion Silencer Select|Ambion|1|RefSeq|64781|siRNA|http://www.invitrogen.com/site/us/en/home/brands/ambion.html?CID=fl-ambion
s3096 siRNA
Ambion Silencer Select|Ambion|1|RefSeq|64781|siRNA|http://www.invitrogen.com/site/us/en/home/brands/ambion.html?CID=fl-ambion
M-006707-00 siRNA_Pool
siGENOME|Thermo Scientific Dharmacon|1|RefSeq release 5-7|84206 siRNAs in pools of four|siRNA|http://www.dharmacon.com/
SP00006315 siRNA_Pool
Druggable and whole genome supplement|Qiagen|1, 3|RefSeq|70308 siRNAs in pools of four|siRNA|http://www.qiagen.com/

Gene information for gene 1158 (CKM)

Gene:
Alternate gene names:M-CK, CKMM
Description:creatine kinase, muscle
Chromosome:19
Start:45809670
Stop:45826234
Strand:negative
Locus:19q13.32
Biotype:protein-coding
Status:live
Entrez Gene:
GeneCards:
Ensembl:
Hgnc:
Hprd:
Mim:
Uniprot:
Vega:
RefSeq:

Genome browser for gene 1158 (CKM)

Homo sapiens GRCh37
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