Daxx mediates the small ubiquitin-like modifier-dependent transcriptional repression of Smad4

Che Chang Chang, Ding Yen Lin, Hsin I. Fang, Ruey Hwa Chen, Hsiu Ming Shih

研究成果: 雜誌貢獻文章

81 引文 (Scopus)

摘要

Daxx has been shown to function as an apoptosis regulator and transcriptional represser via its interaction with various cytoplasmic and nuclear proteins. Here, we showed that Daxx interacts with Smad4 and represses its transcriptional activity via the C-terminal domain of Daxx. In vitro and in vivo interaction studies indicated that the binding of Smad4 to Daxx depends on Smad4 sumoylation. Substitution of Smad4 SUMO conjugation residue lysine 159, but not 113, to arginine not only disrupted Smad4-Daxx interaction but also relieved Daxx-elicited repression of Smad4 transcriptional activity. Furthermore, chromatin immunoprecipitation analyses revealed the recruitment of Daxx to an endogenous, Smad4-targeted promoter in a Lys159 sumoylation-dependent manner. Finally, down-regulation of Daxx expression by RNA interference enhanced transforming growth factor β-induced transcription of reporter and endogenous genes through a Smad4-dependent, but not K159R-Smad4-dependent, manner. Together, these results indicate that Daxx suppresses Smad4-mediated transcriptional activity by direct interaction with the sumoylated Smad4 and identify a novel role of Daxx in regulating transforming growth factor β signaling.
原文英語
頁(從 - 到)10164-10173
頁數10
期刊Journal of Biological Chemistry
280
發行號11
DOIs
出版狀態已發佈 - 三月 18 2005
對外發佈Yes

指紋

Sumoylation
Transforming Growth Factors
Ubiquitin
Transcription
Nuclear Proteins
Lysine
Chromatin
Arginine
Substitution reactions
Genes
Chromatin Immunoprecipitation
RNA
Apoptosis
RNA Interference
Reporter Genes
Down-Regulation

ASJC Scopus subject areas

  • Biochemistry

引用此文

Daxx mediates the small ubiquitin-like modifier-dependent transcriptional repression of Smad4. / Chang, Che Chang; Lin, Ding Yen; Fang, Hsin I.; Chen, Ruey Hwa; Shih, Hsiu Ming.

於: Journal of Biological Chemistry, 卷 280, 編號 11, 18.03.2005, p. 10164-10173.

研究成果: 雜誌貢獻文章

Chang, Che Chang ; Lin, Ding Yen ; Fang, Hsin I. ; Chen, Ruey Hwa ; Shih, Hsiu Ming. / Daxx mediates the small ubiquitin-like modifier-dependent transcriptional repression of Smad4. 於: Journal of Biological Chemistry. 2005 ; 卷 280, 編號 11. 頁 10164-10173.
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abstract = "Daxx has been shown to function as an apoptosis regulator and transcriptional represser via its interaction with various cytoplasmic and nuclear proteins. Here, we showed that Daxx interacts with Smad4 and represses its transcriptional activity via the C-terminal domain of Daxx. In vitro and in vivo interaction studies indicated that the binding of Smad4 to Daxx depends on Smad4 sumoylation. Substitution of Smad4 SUMO conjugation residue lysine 159, but not 113, to arginine not only disrupted Smad4-Daxx interaction but also relieved Daxx-elicited repression of Smad4 transcriptional activity. Furthermore, chromatin immunoprecipitation analyses revealed the recruitment of Daxx to an endogenous, Smad4-targeted promoter in a Lys159 sumoylation-dependent manner. Finally, down-regulation of Daxx expression by RNA interference enhanced transforming growth factor β-induced transcription of reporter and endogenous genes through a Smad4-dependent, but not K159R-Smad4-dependent, manner. Together, these results indicate that Daxx suppresses Smad4-mediated transcriptional activity by direct interaction with the sumoylated Smad4 and identify a novel role of Daxx in regulating transforming growth factor β signaling.",
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AU - Shih, Hsiu Ming

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