Tumor suppressor bromodomain-containing protein 7 cooperates with Smads to promote transforming growth factor-? responses.

ABSTRACT: Smad proteins are central mediators in the canonical transforming growth factor-? (TGF-?) signaling pathway in mammalian cells. We report here that bromodomain-containing protein 7 (BRD7) functions as a novel transcription coactivator for Smads in TGF-? signaling. BRD7 forms a TGF-? inducible complex with Smad3/4 through its N-terminal Smad-binding domain. BRD7 simultaneously binds to acetylated histones to promote Smad-chromatin association, and associates with histone acetyltransferase p300 to enhance Smad transcriptional activity. Ectopic expression of BRD7, but not its mutants defective in Smad binding, enhances TGF-? transcriptional, tumor-suppressing and epithelial-mesenchymal transition responses. Conversely, depletion of BRD7 inhibits TGF-? responses. Thus, our study provides compelling evidence for a new function of BRD7 in fine-tuning TGF-? physiological responses.

SUBMITTER: Liu T 

PROVIDER: S-EPMC5140778 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature