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

J. Biol. Chem., Vol. 280, Issue 1, 118-124, January 7, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/1/118    most recent M405065200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ge, W.-W. Articles by Strong, M. J. Search for Related Content PubMed PubMed Citation Articles by Ge, W.-W. Articles by Strong, M. J. Social Bookmarking                      What's this?

Mutant Copper-Zinc Superoxide Dismutase Binds to and Destabilizes Human Low Molecular Weight Neurofilament mRNA^*

Wei-Wen Ge, Weiyan Wen, Wendy Strong, Cheryl Leystra-Lantz, and Michael J. Strong¶

From the Cell Biology Research Group, Robarts Research Institute, London, Ontario N6A 5K8 and the Department of Clinical Neurological Sciences, The University of Western Ontario, London, Ontario N6A 5A5, Canada

The mechanism by which mutated copper-zinc superoxide dismutase (SOD1) causes familial amyotrophic lateral sclerosis is believed to involve an adverse gain of function, independent of the physiological antioxidant enzymatic properties of SOD1. In this study, we have observed that mutant SOD1 (G41S, G85A, and G93A) but not the wild type significantly reduced the stability of the low molecular weight neurofilament mRNA in a dosage-dependent manner. We have also demonstrated that mutant SOD1 but not the wild type bound directly to the neurofilament mRNA 3'-untranslated region and that the binding was necessary to induce mRNA destabilization. These observations provide an explanation for a novel gain of function in which mutant SOD1 expression in motor neurons alters an intermediate filament protein expression.

Received for publication, May 6, 2004 , and in revised form, October 22, 2004.

^* This work was supported by the Amyotrophic Lateral Sclerosis Association, the Amyotrophic Lateral Sclerosis Society of Canada, and the Canadian Institutes of Health Research/Neuromuscular Research Partnership. 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.

^¶ To whom correspondence should be addressed: Rm. 7OF10, UC-LHSC, 339 Windermere Rd., London, Ontario N6A 5A5, Canada. Tel.: 519-663-3874; Fax: 519-663-3609; E-mail: mstrong{at}uwo.ca.

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

This article has been cited by other articles:

				L. Lu, L. Zheng, L. Viera, E. Suswam, Y. Li, X. Li, A. G. Estevez, and P. H. King Mutant Cu/Zn-Superoxide Dismutase Associated with Amyotrophic Lateral Sclerosis Destabilizes Vascular Endothelial Growth Factor mRNA and Downregulates Its Expression J. Neurosci., July 25, 2007; 27(30): 7929 - 7938. [Abstract] [Full Text] [PDF]

				R. Canete-Soler, K. S. Reddy, D. R. Tolan, and J. Zhai Aldolases A and C Are Ribonucleolytic Components of a Neuronal Complex That Regulates the Stability of the Light-Neurofilament mRNA J. Neurosci., April 27, 2005; 25(17): 4353 - 4364. [Abstract] [Full Text] [PDF]