HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 11, 10164-10173, March 18, 2005

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 280/11/10164    most recent M409161200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chang, C.-C. Articles by Shih, H.-M. Search for Related Content PubMed PubMed Citation Articles by Chang, C.-C. Articles by Shih, H.-M. Social Bookmarking                      What's this?

Daxx Mediates the Small Ubiquitin-like Modifier-dependent Transcriptional Repression of Smad4^*

Che-Chang Chang, Ding-Yen Lin, Hsin-I Fang, Ruey-Hwa Chen¶, and Hsiu-Ming Shih||

From the Graduate Institute of Life Sciences, National Defense Medical Center, the Division of Molecular and Genomic Medicine, National Health Research Institutes, and the ^¶Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, 11529 Taiwan, Republic of China

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 -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 signaling.

Received for publication, August 10, 2004 , and in revised form, January 5, 2005.

^* This work was supported by National Health Research Institutes Intramural Funds Grant MG-093-PP-03 and National Science Council Grants NSC93-3112-B-400-004 and NSC93-2321-B-400-002 (to H.-M. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains a supplemental figure.

^|| To whom correspondence should be addressed. Present address: Institute of Biomedical Sciences, Academia Sinica., 128, Sec. 2, Academia RD, Taipei 11529, Taiwan. Tel.: 886-2-2652-3520; Fax: 886-2-2785-8594; E-mail: hmshih{at}ibms.sinica.edu.tw.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. Tillmanns, C. Otto, E. Jaffray, C. Du Roure, Y. Bakri, L. Vanhille, S. Sarrazin, R. T. Hay, and M. H. Sieweke SUMO Modification Regulates MafB-Driven Macrophage Differentiation by Enabling Myb-Dependent Transcriptional Repression Mol. Cell. Biol., August 1, 2007; 27(15): 5554 - 5564. [Abstract] [Full Text] [PDF]

				I. Meinecke, A. Cinski, A. Baier, M. A. Peters, B. Dankbar, A. Wille, A. Drynda, H. Mendoza, R. E. Gay, R. T. Hay, et al. Modification of nuclear PML protein by SUMO-1 regulates Fas-induced apoptosis in rheumatoid arthritis synovial fibroblasts PNAS, March 20, 2007; 104(12): 5073 - 5078. [Abstract] [Full Text] [PDF]

				S. J. Choi, S. S. Chung, E. J. Rho, H. W. Lee, M. H. Lee, H.-S. Choi, J. H. Seol, S. H. Baek, O. S. Bang, and C. H. Chung Negative Modulation of RXR{alpha} Transcriptional Activity by Small Ubiquitin-related Modifier (SUMO) Modification and Its Reversal by SUMO-specific Protease SUSP1 J. Biol. Chem., October 13, 2006; 281(41): 30669 - 30677. [Abstract] [Full Text] [PDF]

				R. T. Saffert and R. F. Kalejta Inactivating a Cellular Intrinsic Immune Defense Mediated by Daxx Is the Mechanism through Which the Human Cytomegalovirus pp71 Protein Stimulates Viral Immediate-Early Gene Expression. J. Virol., April 1, 2006; 80(8): 3863 - 3871. [Abstract] [Full Text] [PDF]

				M. S. Macauley, W. J. Errington, M. Scharpf, C. D. Mackereth, A. G. Blaszczak, B. J. Graves, and L. P. McIntosh Beads-on-a-String, Characterization of Ets-1 Sumoylated within Its Flexible N-terminal Sequence J. Biol. Chem., February 17, 2006; 281(7): 4164 - 4172. [Abstract] [Full Text] [PDF]

				J. Massague, J. Seoane, and D. Wotton Smad transcription factors Genes & Dev., December 1, 2005; 19(23): 2783 - 2810. [Abstract] [Full Text] [PDF]

				H.-Y. Kuo, C.-C. Chang, J.-C. Jeng, H.-M. Hu, D.-Y. Lin, G. G. Maul, R. P. S. Kwok, and H.-M. Shih SUMO modification negatively modulates the transcriptional activity of CREB-binding protein via the recruitment of Daxx PNAS, November 22, 2005; 102(47): 16973 - 16978. [Abstract] [Full Text] [PDF]

				J. Long, D. Zuo, and M. Park Pc2-mediated Sumoylation of Smad-interacting Protein 1 Attenuates Transcriptional Repression of E-cadherin J. Biol. Chem., October 21, 2005; 280(42): 35477 - 35489. [Abstract] [Full Text] [PDF]