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

J. Biol. Chem., Vol. 281, Issue 19, 13581-13587, May 12, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/19/13581    most recent M601580200v1 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 Caruano-Yzermans, A. L. Articles by Gitlin, J. D. Search for Related Content PubMed PubMed Citation Articles by Caruano-Yzermans, A. L. Articles by Gitlin, J. D. Social Bookmarking                      What's this?

Mechanisms of the Copper-dependent Turnover of the Copper Chaperone for Superoxide Dismutase^*

From the Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110

The copper chaperone for superoxide dismutase (CCS) is an intracellular metallochaperone required for incorporation of copper into the essential antioxidant enzyme copper/zinc superoxide dismutase (SOD1). Nutritional studies have revealed that the abundance of CCS is inversely proportional to the dietary and tissue copper content. To determine the mechanisms of copper-dependent regulation of CCS, copper incorporation into SOD1 and SOD1 enzymatic activity as well as CCS abundance and half-life were determined after metabolic labeling of CCS^-/- fibroblasts transfected with wild-type or mutant CCS. Wild-type CCS restored SOD1 activity in CCS^-/- fibroblasts, and the abundance of this chaperone in these cells was inversely proportional to the copper content of the media, indicating that copper-dependent regulation of CCS is entirely post-translational. Although mutational studies demonstrated no role for CCS Domain I in this copper-dependent regulation, similar analysis of the CXC motif in Domain III revealed a critical role for these cysteine residues in mediating copper-dependent turnover of CCS. Further mutational studies revealed that this CXC-dependent copper-mediated turnover of CCS is independent of the mechanisms of delivery of copper to SOD1 including CCS-SOD1 interaction. Taken together these data demonstrate a mechanism determining the abundance of CCS that is competitive with the process of copper delivery to SOD1, revealing a unique post-translational component of intracellular copper homeostasis.

Received for publication, February 17, 2006 , and in revised form, March 9, 2006.

^* This work was supported by National Institutes of Health Research Grants DK 61763 (to J. D. 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.

¹ To whom correspondence should be addressed: WA University School of Medicine, McDonnell Pediatric Research Bldg., 660 South Euclid Ave., St. Louis, MO 63110. Tel.: 314-286-2764; Fax: 314-286-2784; E-mail: gitlin{at}kids.wustl.edu.

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

This article has been cited by other articles:

				J. B. Proescher, M. Son, J. L. Elliott, and V. C. Culotta Biological effects of CCS in the absence of SOD1 enzyme activation: implications for disease in a mouse model for ALS Hum. Mol. Genet., June 15, 2008; 17(12): 1728 - 1737. [Abstract] [Full Text] [PDF]

				M. L. Turski and D. J. Thiele Drosophila Ctr1A Functions as a Copper Transporter Essential for Development J. Biol. Chem., August 17, 2007; 282(33): 24017 - 24026. [Abstract] [Full Text] [PDF]

				N. Keshelava, E. Davicioni, Z. Wan, L. Ji, R. Sposto, T. J. Triche, and C. P. Reynolds Histone Deacetylase 1 Gene Expression and Sensitization of Multidrug-Resistant Neuroblastoma Cell Lines to Cytotoxic Agents by Depsipeptide J Natl Cancer Inst, July 18, 2007; 99(14): 1107 - 1119. [Abstract] [Full Text] [PDF]