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

J. Biol. Chem., Vol. 282, Issue 17, 12557-12565, April 27, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/17/12557    most recent M609587200v1 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 Correia, J. d. S. Articles by Ulevitch, R. J. Search for Related Content PubMed PubMed Citation Articles by Correia, J. d. S. Articles by Ulevitch, R. J. Social Bookmarking                      What's this?

The Subunit CSN6 of the COP9 Signalosome Is Cleaved during Apoptosis^*

From the Department of Immunology, Scripps Research Institute, La Jolla, California 92037

The COP9 signalosome is a large multiprotein complex that consists of eight subunits termed CSN1–CSN8. The diverse functions of the COP9 complex include regulation of several important intracellular pathways, including the ubiquitin/proteasome system, DNA repair, cell cycle, developmental changes, and some aspects of immune responses. Nod1 is also thought to be an important cytoplasmic receptor involved in innate immune responses. It detects specific motifs of bacterial peptidoglycan, and this results in activation of multiple signaling pathways and changes in cell function. In this report, we performed a yeast two-hybrid screening and discovered that Nod1 interacts with several components of the COP9 signalosome through its CARD domain. Moreover, we observed that activation of the Nod1 apoptotic pathway leads to specific cleavage of the subunit CSN6. This cleavage is concomitant with caspase processing and generates a short amino-terminal peptide of 3 kDa. A complete inhibition of this cleavage was achieved in the presence of the broad spectrum pharmacological inhibitor of apoptosis, Z-VAD. Furthermore, overexpression of CLARP, a specific caspase 8 inhibitor, completely blocked cleavage of CSN6. Taken together, these results suggest a critical role of caspase 8 in the processing of CSN6. Moreover, these findings suggest that CSN6 cleavage may result in modifications of functions of the COP9 complex that are involved in apoptosis.

Received for publication, October 11, 2006 , and in revised form, January 19, 2007.

^* This work was supported by National Institutes of Health Grants AI 15136 and U54 AI 54523 and Novartis Grant SFP 1568 (to R. J. U.). 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.

¹ To whom correspondence should be addressed: Dept. of Immunology, Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037. Tel.: 858-784-8219; Fax: 858-784-8239; E-mail: ulevitch{at}scripps.edu.

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

This article has been cited by other articles:

				J. da Silva Correia, Y. Miranda, N. Leonard, and R. Ulevitch SGT1 is essential for Nod1 activation PNAS, April 17, 2007; 104(16): 6764 - 6769. [Abstract] [Full Text] [PDF]