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

J. Biol. Chem., Vol. 281, Issue 1, 303-312, January 6, 2006

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 281/1/303    most recent M509060200v1 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 Xu, Z. Articles by Greene, L. A. Search for Related Content PubMed PubMed Citation Articles by Xu, Z. Articles by Greene, L. A. Social Bookmarking                      What's this?

Siah1 Interacts with the Scaffold Protein POSH to Promote JNK Activation and Apoptosis^*

Zhiheng Xu1, Andrew Sproul¶, Wenyi Wang, Nikolay Kukekov, and Lloyd A. Greene

From the Department of Pathology and Center for Neurobiology and Behavior and ^¶Department of Biological Sciences, College of Physicians and Surgeons, Columbia University, New York, New York 10032 and the Key Laboratory of Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 100080 Beijing, China

Siah proteins are ubiquitin-protein isopeptide ligases (E3) that have been implicated in a variety of cellular actions, including promotion of apoptotic death. Here, we show that Siah1 is a binding partner for POSH (plenty of SH3s), a scaffold component of the apoptotic JNK pathway, and that Siah contributes to death of neurons and other cell types by activating the JNK pathway. Such proapoptotic activity requires the E3 ligase activity of Siah1. Moreover, apoptotic stimuli markedly elevate cellular Siah1 levels by a mechanism reliant on Siah1 protein stabilization. This stabilization requires JNK pathway activation and interaction with POSH and is enhanced by phosphorylation of SIAH1 at tyrosines 100 and 126. Depletion of intracellular Siah proteins via small interference RNA partially protects cells from death evoked by apoptotic stimuli such as trophic factor deprivation and DNA damage. These findings thus reveal a "loop" mechanism in which the JNK pathway promotes SIAH1 stabilization and in which SIAH1 in turn activates the JNK pathway and, ultimately, contributes to cell death.

Received for publication, August 17, 2005 , and in revised form, October 17, 2005.

^* This work was supported by grants from NINDS, National Institutes of Health and the Blanchette Rockefeller Foundation (to L. A. G.). 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–S5.

¹ To whom correspondence should be addressed: Dept. of Pathology, Columbia University, P&S 15-401, 630 West 168th St., New York, NY 10032. Tel.: 212-305-6370; Fax: 212-305-5498; E-mail: zhxu{at}genetics.ac.cn.

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

This article has been cited by other articles:

				R. Abada, T. Dreyfuss-Grossman, Y. Herman-Bachinsky, H. Geva, S.-R. Masa, and R. Sarid SIAH-1 Interacts with the Kaposi's Sarcoma-Associated Herpesvirus-Encoded ORF45 Protein and Promotes Its Ubiquitylation and Proteasomal Degradation J. Virol., March 1, 2008; 82(5): 2230 - 2240. [Abstract] [Full Text] [PDF]

				S. Yun, A. Moller, S.-K. Chae, W.-P. Hong, Y. J. Bae, D. D. L. Bowtell, S. H. Ryu, and P.-G. Suh Siah Proteins Induce the Epidermal Growth Factor-dependent Degradation of Phospholipase C{epsilon} J. Biol. Chem., January 11, 2008; 283(2): 1034 - 1042. [Abstract] [Full Text] [PDF]

				T. R. Lyons, J. Thorburn, P. W. Ryan, A. Thorburn, S. M. Anderson, and C. K. Kassenbrock Regulation of the Pro-apoptotic Scaffolding Protein POSH by Akt J. Biol. Chem., July 27, 2007; 282(30): 21987 - 21997. [Abstract] [Full Text] [PDF]

				S. Tuvia, D. Taglicht, O. Erez, I. Alroy, I. Alchanati, V. Bicoviski, M. Dori-Bachash, D. Ben-Avraham, and Y. Reiss The ubiquitin E3 ligase POSH regulates calcium homeostasis through spatial control of Herp J. Cell Biol., April 9, 2007; 177(1): 51 - 61. [Abstract] [Full Text] [PDF]

				M. Wilhelm, Z. Xu, N. V. Kukekov, S. Gire, and L. A. Greene Proapoptotic Nix Activates the JNK Pathway by Interacting with POSH and Mediates Death in a Parkinson Disease Model J. Biol. Chem., January 12, 2007; 282(2): 1288 - 1295. [Abstract] [Full Text] [PDF]

				A. Khurana, K. Nakayama, S. Williams, R. J. Davis, T. Mustelin, and Z. Ronai Regulation of the Ring Finger E3 Ligase Siah2 by p38 MAPK J. Biol. Chem., November 17, 2006; 281(46): 35316 - 35326. [Abstract] [Full Text] [PDF]

				S. Kondo, S. Y. Seo, T. Yoshizaki, N. Wakisaka, M. Furukawa, I. Joab, K. L. Jang, and J. S. Pagano EBV Latent Membrane Protein 1 Up-regulates Hypoxia-Inducible Factor 1{alpha} through Siah1-Mediated Down-regulation of Prolyl Hydroxylases 1 and 3 in Nasopharyngeal Epithelial Cells. Cancer Res., October 15, 2006; 66(20): 9870 - 9877. [Abstract] [Full Text] [PDF]