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.
Keywords:
SMAD Transcription Factor; Signal Transduction; Transcription Repressor; Transforming Growth Factor β (TGFβ); Zinc Finger.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylation
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Aminoacyltransferases
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E1A-Associated p300 Protein / genetics
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E1A-Associated p300 Protein / metabolism
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HEK293 Cells
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HeLa Cells
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Histones / genetics
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Histones / metabolism
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Humans
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Signal Transduction / physiology*
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Smad3 Protein / genetics
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Smad3 Protein / metabolism*
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Smad4 Protein / genetics
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Smad4 Protein / metabolism*
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transforming Growth Factor beta / genetics
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Transforming Growth Factor beta / metabolism*
Substances
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Histones
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Repressor Proteins
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SMAD3 protein, human
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SMAD4 protein, human
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Smad3 Protein
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Smad4 Protein
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Transcription Factors
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Transforming Growth Factor beta
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E1A-Associated p300 Protein
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EP300 protein, human
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Aminoacyltransferases
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ZNF451 protein, human