Gene Set: CEBALLOS_TARGETS_OF_TP53_AND_MYC_UP

Standard name CEBALLOS_TARGETS_OF_TP53_AND_MYC_UP
Systematic name M1247
Brief description Genes up-regulated in K562 cells (chronic myelogenous leukemia, CML) expressing TP53 and MYC [GeneID=7157;4609].
Full description or abstract We have previously demonstrated that c-Myc impairs p53-mediated apoptosis in K562 human leukemia cells, which lack ARF. To investigate the mechanisms by which c-Myc protects from p53-mediated apoptosis, we used K562 cells that conditionally express c-Myc and harbor a temperature-sensitive allele of p53. Gene expression profiles of cells expressing wild-type conformation p53 in the presence of either uninduced or induced c-Myc were analysed by cDNA microarrays. The results show that multiple p53 target genes are downregulated when c-Myc is present, including p21WAF1, MDM2, PERP, NOXA, GADD45, DDB2, PIR121 and p53R2. Also, a number of genes that are upregulated by c-Myc in cells expressing wild-type conformation p53 encode chaperones related to cell death protection as HSP105, HSP90 and HSP27. Both downregulation of p53 target genes and upregulation of chaperones could explain the inhibition of apoptosis observed in K562 cells with ectopic c-Myc. Myc-mediated impairment of p53 transactivation was not restricted to K562 cells, but it was reproduced in a panel of human cancer cell lines derived from different tissues. Our data suggest that elevated levels of Myc counteract p53 activity in human tumor cells that lack ARF. This mechanism could contribute to explain the c-Myc deregulation frequently found in cancer.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 15856024   Authors: Ceballos E,Muñoz-Alonso MJ,Berwanger B,Acosta JC,Hernández R,Krause M,Hartmann O,Eilers M,León J
Exact source Table 3
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(show 8 gene sets from the same authors)
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Organism Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
Source platform HUMAN_SEQ_ACCESSION
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Version history 3.1: First introduced

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