TableEdit

Drost, J, Mantovani, F, Tocco, F, Elkon, R, Comel, A, Holstege, H, Kerkhoven, R, Jonkers, J, Voorhoeve, PM, Agami, R and Del Sal, G (2010) BRD7 is a candidate tumour suppressor gene required for p53 function. Nat. Cell Biol. 12:380-9

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.

PubMed Online version:10.1038/ncb2038

Acetylation; Binding Sites; Breast Neoplasms/genetics; Breast Neoplasms/metabolism; Breast Neoplasms/pathology; Cell Aging/genetics; Cell Line, Tumor; Cell Proliferation; Cell Transformation, Neoplastic/genetics; Cell Transformation, Neoplastic/metabolism; Chromosomal Proteins, Non-Histone/genetics; Chromosomal Proteins, Non-Histone/metabolism; Female; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Genes, ras; Histones/metabolism; Humans; Mutation; Promoter Regions, Genetic; Protein Binding; RNA Interference; Recombinant Fusion Proteins/metabolism; Time Factors; Transcription, Genetic; Tumor Suppressor Protein p53/genetics; Tumor Suppressor Protein p53/metabolism; p300-CBP Transcription Factors/metabolism