Daxx Mediates the Small Ubiquitin-like Modifier-dependent Transcriptional Repression of Smad4
Open Access
- 1 March 2005
- journal article
- Published by Elsevier BV
- Vol. 280 (11), 10164-10173
- https://doi.org/10.1074/jbc.m409161200
Abstract
Daxx has been shown to function as an apoptosis regulator and transcriptional repressor 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.Keywords
This publication has 64 references indexed in Scilit:
- SUMOylation regulates nucleo-cytoplasmic shuttling of Elk-1The Journal of cell biology, 2004
- Protein Modification by SUMOAnnual Review of Biochemistry, 2004
- SUMO and transcriptional regulationSeminars in Cell & Developmental Biology, 2004
- SUMO Promotes HDAC-Mediated Transcriptional RepressionMolecular Cell, 2004
- Nuclear and unclear functions of SUMONature Reviews Molecular Cell Biology, 2003
- Versatile protein tag, SUMO: Its enzymology and biological functionJournal of Cellular Physiology, 2002
- SP-RING for SUMOCell, 2001
- Protein modification by SUMOTrends in Biochemical Sciences, 2001
- How cells read TGF-β signalsNature Reviews Molecular Cell Biology, 2000
- SUMO-1 Modification of IκBα Inhibits NF-κB ActivationMolecular Cell, 1998