Tumor suppressor bromodomain-containing protein 7 cooperates with Smads to promote transforming growth factor-β responses.
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 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.
Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China.|Department of Cell Biology and Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
Ting
T
Liu
Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China.
Meiling
M
Zhao
Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China.
Jinquan
J
Liu
Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China.
Zhou
Z
He
Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China.
Ye
Y
Zhang
State Key Laboratory of Cellular Stress Biology and Innovation Center for Cell Signaling Network, College of Life Sciences, Xiamen, Fujian 361102, China.
Han
H
You
Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China.
Jun
J
Huang
Michael E. DeBakey Department of Surgery and Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Xia
X
Lin
Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China.|Michael E. DeBakey Department of Surgery and Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Xin-Hua
XH
Feng
D000072283:A549 Cells; D000107:Acetylation; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D057809:HEK293 Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D051379:Mice; D051785:Smad Proteins / Q000235:genetics*; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D050880:p300-CBP Transcription Factors / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor; D000092468:Bromodomain Containing Proteins
D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C485694:BRD7 protein, human; D000092468:Bromodomain Containing Proteins