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

Research output: Contribution to journalArticle

81 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)10164-10173
Number of pages10
JournalJournal of Biological Chemistry
Volume280
Issue number11
DOIs
Publication statusPublished - Mar 18 2005
Externally publishedYes

Fingerprint

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

Cite this

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.

In: Journal of Biological Chemistry, Vol. 280, No. 11, 18.03.2005, p. 10164-10173.

Research output: Contribution to journalArticle

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. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 11. pp. 10164-10173.
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