Tumor suppressor bromodomain-containing protein 7 cooperates with Smads to promote transforming growth factor-β responses
| Autor: | Ting Liu, Jun Huang, Ye Zhang, Jinquan Liu, Meiling Zhao, Zhou He, Xin-Hua Feng, Xia Lin, Han You |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research Transcription Genetic Chromosomal Proteins Non-Histone Transcription coactivator Smad Proteins SMAD Biology Article Cell Line Histones Mice 03 medical and health sciences 0302 clinical medicine Growth factor receptor Transforming Growth Factor beta Genetics Animals Humans SMAD binding p300-CBP Transcription Factors Molecular Biology Smad Cell Proliferation Histone Acetyltransferase p300 Binding Sites Acetylation Bromodomain Cell biology HEK293 Cells 030104 developmental biology Gene Expression Regulation A549 Cells 030220 oncology & carcinogenesis Transcription Coactivator Signal transduction BRD7 Transforming growth factor |
| Zdroj: | Oncogene |
| ISSN: | 1476-5594 0950-9232 |
| Popis: | Smad proteins are central mediators in the canonical transforming growth factor-β (TGF-β) signaling pathway in mammalian cells. We report here that bromodomain-containing protein 7 (BRD7) functions as a novel transcription coactivator for Smads in TGF-β signaling. BRD7 forms a TGF-β 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-β transcriptional, tumor suppressing and epithelial-mesenchymal transition (EMT) responses. Conversely, depletion of BRD7 inhibits TGF-β responses. Thus, our study provides compelling evidence for a new function of BRD7 in fine-tuning TGF-β physiological responses. |
| Databáze: | OpenAIRE |
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