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Originally published In Press as doi:10.1074/jbc.M203300200 on July 16, 2002

J. Biol. Chem., Vol. 277, Issue 38, 35071-35079, September 20, 2002
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Staring, a Novel E3 Ubiquitin-Protein Ligase That Targets Syntaxin 1 for Degradation*

Lih-Shen ChinDagger §, John P. Vavalle§, and Lian LiDagger §

From the Dagger  Department of Pharmacology, Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, Georgia 30322-3090 and § Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599

Syntaxin 1 is an essential component of the neurotransmitter release machinery, and regulation of syntaxin 1 expression levels is thought to contribute to the mechanism underlying learning and memory. However, the molecular events that control the degradation of syntaxin 1 remain undefined. Here we report the identification and characterization of a novel RING finger protein, Staring, that interacts with syntaxin 1. Staring is expressed throughout the brain, where it exists in both cytosolic and membrane-associated pools. Staring binds and recruits the brain-enriched E2 ubiquitin-conjugating enzyme UbcH8 to syntaxin 1 and facilitates the ubiquitination and proteasome-dependent degradation of syntaxin 1. These findings suggest that Staring is a novel E3 ubiquitin-protein ligase that targets syntaxin 1 for degradation by the ubiquitin-proteasome pathway.

* This work was supported by the University Research Committee of Emory University and by a University of North Carolina Junior Faculty Development Award and Medical Faculty Award (to L.-S. C.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AF352815.

To whom correspondence should be addressed: Dept. of Pharmacology, Emory University School of Medicine, 1510 Clifton Rd., Atlanta, GA 30322-3090. Tel.: 404-727-5987; Fax: 404-727-0365; E-mail: lianli@pharm.emory.edu.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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