Gene regulation and tumor suppression by the bromodomain-containing protein BRD7.
Oncogene-induced senescence (OIS) is a cellular defense mechanism against excessive mitogenic signaling and tumorigenesis. One of the major pathways required for OIS is the p53 tumor suppressor pathway. Consequently, many human tumors harbor p53 mutations while others show a dysfunctional p53 pathway, frequently by unknown mechanisms. We recently identified BRD7 as a potential tumor suppressor gene acting as a transcriptional cofactor for p53, affecting histone acetylation, p53 acetylation, and promoter activity on a subset of p53 target genes. We further found low BRD7 expression specifically in a subgroup of human breast tumors harboring wild-type, but not mutant, p53 and showed that one of the responsible mechanisms is deletion of the BRD7 gene locus. Here we further discuss the role of BRD7 as a cofactor in transcriptional regulation and highlight its role as a tumor suppressor via association with p53 and other tumor suppressor proteins.
Mantovani
Fiamma
F
Laboratorio Nazionale CIB, Area Science Park, Trieste, Italy.
Drost
Jarno
J
Voorhoeve
P Mathijs
PM
Del Sal
Giannino
G
Agami
Reuven
R
D000107:Acetylation; D049109:Cell Proliferation; D016922:Cellular Senescence; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000378:metabolism*; D004260:DNA Repair; D005786:Gene Expression Regulation; D006801:Humans; D014157:Transcription Factors / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000378:metabolism*; D000092468:Bromodomain Containing Proteins
D002868:Chromosomal Proteins, Non-Histone; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C485694:BRD7 protein, human; D000092468:Bromodomain Containing Proteins; C445179:SWI-SNF-B chromatin-remodeling complex