Human Gene Set: SCIAN_CELL_CYCLE_TARGETS_OF_TP53_AND_TP73_DN


Standard name SCIAN_CELL_CYCLE_TARGETS_OF_TP53_AND_TP73_DN
Systematic name M9402
Brief description Cell cycle genes down-regulated in H1299 cells (lung cancer) after overexpression of either P53 or P73 [GeneID=7157;7161].
Full description or abstract When normal cells come under stress, the wild-type (WT) p53 level increases resulting in the regulation of gene expression responsible for growth arrest or apoptosis. Here we show that elevated levels of WT p53 or its homologue, p73, inhibit expression of a number of cell cycle regulatory and growth promoting genes. Our analysis also identified a group of genes whose expression is differentially regulated by WT p53 and p73. We have infected p53-null H1299 human lung carcinoma cells with recombinant adenoviruses expressing WT p53, p73 or beta-galactosidase, and have undertaken microarray hybridization analyses to identify genes whose expression profile is altered by p53 or p73. Quantitative real-time PCR verified the repression of E2F-5, centromere protein A and E, minichromosome maintenance proteins (MCM)-2, -3, -5, -6 and -7 and human CDC25B after p53 expression. 5-Fluorouracil treatment of colon carcinoma HCT116 cells expressing WT p53 results in a reduction of the cyclin B2 protein level suggesting that DNA damage may indeed cause repression of these genes. Transient transcriptional assays verified that WT p53 repressed promoters of a number of these genes. Interestingly, a gain-of-function p53 mutant instead upregulated a number of these promoters in transient transfection. Using promoter deletion mutants of MCM-7 we have found that WT p53-mediated repression needs a minimal promoter that contains a single E2F site and surrounding sequences. However, a single E2F site cannot be significantly repressed by WT p53. Many of the genes identified are also repressed by p21. Thus, our work shows that WT p53 and p73 repress a number of growth-related genes and that in many instances this repression may be through the induction of p21.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 17982488   Authors: Scian MJ,Carchman EH,Mohanraj L,Stagliano KE,Anderson MA,Deb D,Crane BM,Kiyono T,Windle B,Deb SP,Deb S
Exact source Table 1: selected by p53
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Source species Homo sapiens
Contributed by Jessica Robertson (MSigDB Team)
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identifier namespace		 HUMAN_SEQ_ACCESSION
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Version history 3.0: First introduced

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