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

J. Biol. Chem., Vol. 282, Issue 13, 9475-9481, March 30, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/13/9475    most recent M700875200v1 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 Kajino, T. Articles by Ninomiya-Tsuji, J. Search for Related Content PubMed PubMed Citation Articles by Kajino, T. Articles by Ninomiya-Tsuji, J. Social Bookmarking                      What's this?

TAK1 MAPK Kinase Kinase Mediates Transforming Growth Factor- Signaling by Targeting SnoN Oncoprotein for Degradation^*

Taisuke Kajino, Emily Omori, Shunsuke Ishii^¶, Kunihiro Matsumoto^||, and Jun Ninomiya-Tsuji^||1

From the Department of Molecular Biology, Graduate School of Science, Nagoya University, Nagoya 464-8602, Japan, the Department of Environmental and Molecular Toxicology, North Carolina State University, Raleigh, North Carolina 27695-7633, ^¶Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, Ibaraki 305-0074, Japan, and ^||Solution Oriented Research for Science and Technology, Japan Science and Technology Agency, Japan

Transforming growth factor- (TGF-) regulates a variety of physiologic processes through essential intracellular mediators Smads. The SnoN oncoprotein is an inhibitor of TGF- signaling. SnoN recruits transcriptional repressor complex to block Smad-dependent transcriptional activation of TGF--responsive genes. Following TGF- stimulation, SnoN is rapidly degraded, thereby allowing the activation of TGF- target genes. Here, we report the role of TAK1 as a SnoN protein kinase. TAK1 interacted with and phosphorylated SnoN, and this phosphorylation regulated the stability of SnoN. Inactivation of TAK1 prevented TGF--induced SnoN degradation and impaired induction of the TGF--responsive genes. These data suggest that TAK1 modulates TGF--dependent cellular responses by targeting SnoN for degradation.

Received for publication, January 30, 2007

^* This work was supported by special grants for advanced research on cancer from the Ministry of Education, Culture, and Science of Japan (to K. M.) and by National Institutes of Health Grants GM068812 and AR050972 (to J. N.-T.). 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 supplemental Figs. S1–S3.

¹ To whom correspondence should be addressed: Dept. of Environmental and Molecular Toxicology, North Carolina State University, Raleigh, NC 27695-7633. Tel.: 919-513-1586; Fax: 919-515-7169; E-mail: Jun_Tsuji{at}ncsu.edu.

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

This article has been cited by other articles:

				M. Erdogan, A. Pozzi, N. Bhowmick, H. L. Moses, and R. Zent Transforming Growth Factor-{beta} (TGF-{beta}) and TGF-{beta}-Associated Kinase 1 Are Required for R-Ras-Mediated Transformation of Mammary Epithelial Cells Cancer Res., August 1, 2008; 68(15): 6224 - 6231. [Abstract] [Full Text] [PDF]

				R. Kajino-Sakamoto, M. Inagaki, E. Lippert, S. Akira, S. Robine, K. Matsumoto, C. Jobin, and J. Ninomiya-Tsuji Enterocyte-Derived TAK1 Signaling Prevents Epithelium Apoptosis and the Development of Ileitis and Colitis J. Immunol., July 15, 2008; 181(2): 1143 - 1152. [Abstract] [Full Text] [PDF]

				S. I. Kim, J. H. Kwak, L. Wang, and M. E. Choi Protein Phosphatase 2A Is a Negative Regulator of Transforming Growth Factor-{beta}1-induced TAK1 Activation in Mesangial Cells J. Biol. Chem., April 18, 2008; 283(16): 10753 - 10763. [Abstract] [Full Text] [PDF]