A member of the ETS family, EHF, and the ATPase RUVBL1 inhibit p53-mediated apoptosis.

ABSTRACT: Tumour cells are known to be dependent on, or 'addicted to', not only oncogenes, but also some non-oncogenes. However, the mechanisms by which tumour cells are addicted to these genes have not been fully explained. Here, we show that overexpression of a member of the ETS family, EHF, is required for the survival of colon tumour cells that contain wild-type p53. We found that EHF directly activates the transcription of RUVBL1, an ATPase associated with chromatin-remodelling complexes. RUVBL1 blocks p53-mediated apoptosis by repressing the expression of p53 and its target genes. Moreover, we found that RUVBL1 represses p53 transcription by binding to the p53 promoter, interfering with RNF20/hBRE1-mediated histone H2B monoubiquitination and promoting PAF1-mediated histone H3K9 trimethylation.

SUBMITTER: Taniue K 

PROVIDER: S-EPMC3128968 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature