STANDARD_NAME SCIAN_CELL_CYCLE_TARGETS_OF_TP53_AND_TP73_DN SYSTEMATIC_NAME M9402 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/SCIAN_CELL_CYCLE_TARGETS_OF_TP53_AND_TP73_DN NAMESPACE HUMAN_SEQ_ACCESSION DESCRIPTION_BRIEF Cell cycle genes down-regulated in H1299 cells (lung cancer) after overexpression of either P53 or P73 [GeneID=7157;7161]. DESCRIPTION_FULL 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. PMID 17982488 GEOID AUTHORS Scian MJ,Carchman EH,Mohanraj L,Stagliano KE,Anderson MA,Deb D,Crane BM,Kiyono T,Windle B,Deb SP,Deb S CONTRIBUTOR Jessica Robertson CONTRIBUTOR_ORG MSigDB Team EXACT_SOURCE Table 1: selected by p53 FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS AB017430,D55716,L16991,L25876,M13929,M25753,M34065,M68520,NM_001255,NM_001827,NM_003600,NM_004856,NM_005915,NM_006325,NM_012112,NM_014268,NM_015714,NM_016426,S78187,U73379,X51688,Z36714 GENE_SYMBOLS KIF22,MCM7,DTYMK,CDKN3,MYC,CCNB1,CDC25C,CDK2,CDC20,CKS2,AURKA,KIF23,MCM6,RAN,TPX2,MAPRE2,G0S2,GTSE1,CDC25B,UBE2C,CCNA2,CCNF FOUNDER_NAMES