STANDARD_NAME	SCIAN_INVERSED_TARGETS_OF_TP53_AND_TP73_UP
SYSTEMATIC_NAME	M7918
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/SCIAN_INVERSED_TARGETS_OF_TP53_AND_TP73_UP
NAMESPACE	HUMAN_SEQ_ACCESSION
DESCRIPTION_BRIEF	Genes that were inversely correlated in H1299 cells (lung cancer): up-regulated by P53 [GeneID=7157] and down-regulated by P73 [GeneID=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 S2b: up by p53 and down by p73b
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	J05614,NM_000146,NM_000285,NM_003533,NM_004212,NM_005281,NM_006278,NM_016116,NM_016155,NM_020485,X02469
GENE_SYMBOLS	PCNA,FTL,PEPD,H3C11,SLC28A2,GPR3,ST3GAL4,ASB4,MMP17,RHCE,TP53
FOUNDER_NAMES