STANDARD_NAME ONGUSAHA_BRCA1_TARGETS_DN SYSTEMATIC_NAME M2068 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/ONGUSAHA_BRCA1_TARGETS_DN NAMESPACE MOUSE_SEQ_ACCESSION DESCRIPTION_BRIEF Genes down-regulated in MEF cells (embryonic fibroblast) lacking TP53 and BRCA1 [GeneID=7157;672] by expression of BRCA1. DESCRIPTION_FULL The tumor suppressor protein BRCA1 has been shown to enhance p53 transcription, whereas activated p53 represses BRCA1 transcription. To further understand the functional interaction of these proteins, we investigated the role of BRCA1 in p53-induced phenotypes. We found that BRCA1 when subjected to forced expression acts synergistically with wild-type p53, resulting in irreversible growth arrest, as shown by VhD mouse fibroblast cells expressing a temperature-sensitive mutant of p53. Furthermore, reintroduction of both BRCA1 and p53 into BRCA1(-/-)/p53(-/-) mouse embryonic fibroblasts markedly increased the senescence phenotype compared to that induced by p53 alone. In particular, we found that BRCA1 expression attenuated p53-mediated cell death in response to gamma-irradiation. Moreover, microarray screening of 11 000 murine genes demonstrated that a set of genes upregulated by p53 is enhanced by coexpression of BRCA1 and p53, suggesting that BRCA1 and p53 exert a promoter selectivity leading to a specific phenotype. Taken together, our results provide evidence that BRCA1 is involved in p53-mediated growth suppression rather than apoptosis. PMID 12802282 GEOID AUTHORS Ongusaha PP,Ouchi T,Kim KT,Nytko E,Kwak JC,Duda RB,Deng CX,Lee SW CONTRIBUTOR Arthur Liberzon CONTRIBUTOR_ORG MSigDB Team EXACT_SOURCE Table 2: Downregulated genes FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS AA727482,AA982124,AF041847,AI595322,AI843564,AI847972,AW049254,AW049275,AW049619,D83033,U67160,U89352,X70058,X76850,Z67747 GENE_SYMBOLS SCEL,,ANKRD1,,TPR,,,DUSP12,CDK8,ZNF638,ARHGAP5,LYPLA1,CCL7,MAPKAPK2,ZFP62 FOUNDER_NAMES