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http://purl.uniprot.org/citations/17417969http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/17417969http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/17417969http://www.w3.org/2000/01/rdf-schema#comment"

Background

The retinoblastoma tumor suppressor (Rb) acts in a conserved pathway that is deregulated in most human cancers. Inactivation of the single Rb-related gene in Caenorhabditis elegans, lin-35, has only limited effects on viability and fertility, yet causes changes in cell-fate and cell-cycle regulation when combined with inactivation of specific other genes. For instance, lin-35 Rb is a synthetic multivulva (synMuv) class B gene, which causes a multivulva phenotype when inactivated simultaneously with a class A or C synMuv gene.

Results

We used the ORFeome RNAi library to identify genes that interact with C. elegans lin-35 Rb and identified 57 genes that showed synthetic or enhanced RNAi phenotypes in lin-35 mutants as compared to rrf-3 and eri-1 RNAi hypersensitive mutants. Based on characterizations of a deletion allele, the synthetic lin-35 interactor zfp-2 was found to suppress RNAi and to cooperate with lin-35 Rb in somatic gonad development. Interestingly, ten splicing-related genes were found to function similar to lin-35 Rb, as synMuv B genes that prevent inappropriate vulval induction. Partial inactivation of specific spliceosome components revealed further similarities with lin-35 Rb functions in cell-cycle control, transgene expression and restricted expression of germline granules.

Conclusion

We identified an extensive series of candidate lin-35 Rb interacting genes and validated zfp-2 as a novel lin-35 synthetic lethal gene. In addition, we observed a novel role for a subset of splicing components in lin-35 Rb-controlled processes. Our data support novel hypotheses about possibilities for anti-cancer therapies and multilevel regulation of gene expression."xsd:string
http://purl.uniprot.org/citations/17417969http://purl.org/dc/terms/identifier"doi:10.1186/1471-213x-7-30"xsd:string
http://purl.uniprot.org/citations/17417969http://purl.org/dc/terms/identifier"doi:10.1186/1471-213x-7-30"xsd:string
http://purl.uniprot.org/citations/17417969http://purl.uniprot.org/core/author"Vidal M."xsd:string
http://purl.uniprot.org/citations/17417969http://purl.uniprot.org/core/author"Vidal M."xsd:string
http://purl.uniprot.org/citations/17417969http://purl.uniprot.org/core/author"Chandra A."xsd:string
http://purl.uniprot.org/citations/17417969http://purl.uniprot.org/core/author"Chandra A."xsd:string
http://purl.uniprot.org/citations/17417969http://purl.uniprot.org/core/author"van den Heuvel S."xsd:string
http://purl.uniprot.org/citations/17417969http://purl.uniprot.org/core/author"van den Heuvel S."xsd:string
http://purl.uniprot.org/citations/17417969http://purl.uniprot.org/core/author"Ceron J."xsd:string
http://purl.uniprot.org/citations/17417969http://purl.uniprot.org/core/author"Ceron J."xsd:string
http://purl.uniprot.org/citations/17417969http://purl.uniprot.org/core/author"Rual J.F."xsd:string
http://purl.uniprot.org/citations/17417969http://purl.uniprot.org/core/author"Rual J.F."xsd:string
http://purl.uniprot.org/citations/17417969http://purl.uniprot.org/core/author"Dupuy D."xsd:string
http://purl.uniprot.org/citations/17417969http://purl.uniprot.org/core/author"Dupuy D."xsd:string
http://purl.uniprot.org/citations/17417969http://purl.uniprot.org/core/date"2007"xsd:gYear
http://purl.uniprot.org/citations/17417969http://purl.uniprot.org/core/date"2007"xsd:gYear
http://purl.uniprot.org/citations/17417969http://purl.uniprot.org/core/name"BMC Dev. Biol."xsd:string
http://purl.uniprot.org/citations/17417969http://purl.uniprot.org/core/name"BMC Dev. Biol."xsd:string
http://purl.uniprot.org/citations/17417969http://purl.uniprot.org/core/pages"30"xsd:string
http://purl.uniprot.org/citations/17417969http://purl.uniprot.org/core/pages"30"xsd:string
http://purl.uniprot.org/citations/17417969http://purl.uniprot.org/core/title"Large-scale RNAi screens identify novel genes that interact with the C. elegans retinoblastoma pathway as well as splicing-related components with synMuv B activity."xsd:string
http://purl.uniprot.org/citations/17417969http://purl.uniprot.org/core/title"Large-scale RNAi screens identify novel genes that interact with the C. elegans retinoblastoma pathway as well as splicing-related components with synMuv B activity."xsd:string
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