BRD7 is a candidate tumour suppressor gene required for p53 function

Jarno Drost, Fiamma Mantovani, Francesca Tocco, Ran Elkon, Anna Comel, Henne Holstege, Ron Kerkhoven, Jos Jonkers, P Mathijs Voorhoeve, Reuven Agami, Giannino Del Sal

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

Samenvatting

Oncogene-induced senescence is a p53-dependent defence mechanism against uncontrolled proliferation. Consequently, many human tumours harbour p53 mutations and others show a dysfunctional p53 pathway, frequently by unknown mechanisms. Here we identify BRD7 (bromodomain-containing 7) as a protein whose inhibition allows full neoplastic transformation in the presence of wild-type p53. In human breast tumours harbouring wild-type, but not mutant, p53 the BRD7 gene locus was frequently deleted and low BRD7 expression was found in a subgroup of tumours. Functionally, BRD7 is required for efficient p53-mediated transcription of a subset of target genes. BRD7 interacts with p53 and p300 and is recruited to target gene promoters, affecting histone acetylation, p53 acetylation and promoter activity. Thus, BRD7 suppresses tumorigenicity by serving as a p53 cofactor required for the efficient induction of p53-dependent oncogene-induced senescence.

Originele taal-2Engels
Pagina's (van-tot)380-9
Aantal pagina's10
TijdschriftNature cell biology
Volume12
Nummer van het tijdschrift4
DOI's
StatusGepubliceerd - apr. 2010
Extern gepubliceerdJa

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