title: Zinc finger protein 451 is a novel Smad corepressor in transforming growth factor-β signaling.
abstract: ZNF451 is a transcriptional cofactor localized to promyelocytic leukemia bodies. Here, we present evidence demonstrating that ZNF451 physically interacts with Smad3/4 and functionally inhibits TGF-β signaling. Increased expression of ZNF451 attenuates TGF-β-induced growth inhibitory and gene transcriptional responses, whereas depletion of ZNF451 enhances TGF-β responses. Mechanistically, ZNF451 blocks the ability of Smad3/4 to recruit p300 in response to TGF-β, which causes reduction of histone H3K9 acetylation on the promoters of TGF-β target genes. Taken together, ZNF451 acts as a transcriptional corepressor for Smad3/4 and negatively regulates TGF-β signaling.
authors: From the Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China and.
authors: Yili
authors: Y
authors: Feng
authors: Hongxing
authors: H
authors: Wu
authors: Yongxian
authors: Y
authors: Xu
authors: Zhengmao
authors: Z
authors: Zhang
authors: Ting
authors: T
authors: Liu
authors: Xia
authors: X
authors: Lin
authors: Xin-Hua
authors: XH
authors: Feng
mesh_terms: D000107:Acetylation; D019881:Aminoacyltransferases; D050881:E1A-Associated p300 Protein / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism*; D051901:Smad4 Protein / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
chemical_list: D006657:Histones; D012097:Repressor Proteins; C497790:SMAD3 protein, human; C497796:SMAD4 protein, human; D051900:Smad3 Protein; D051901:Smad4 Protein; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; D019881:Aminoacyltransferases; C531551:ZNF451 protein, human
keywords: SMAD Transcription Factor; Signal Transduction; Transcription Repressor; Transforming Growth Factor β (TGFβ); Zinc Finger