Staring, a novel E3 ubiquitin-protein ligase that targets syntaxin 1 for degradation.
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.
Department of Pharmacology, Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, Georgia 30322-3090, USA.
Lih-Shen
LS
Chin
John P
JP
Vavalle
Lian
L
Li
D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism*; D015152:Blotting, Northern; D015153:Blotting, Western; D003001:Cloning, Molecular; D018076:DNA, Complementary; D006801:Humans; D006868:Hydrolysis; D008025:Ligases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D051381:Rats; D017386:Sequence Homology, Amino Acid; D050827:Syntaxin 1; D044767:Ubiquitin-Protein Ligases
D000954:Antigens, Surface; D018076:DNA, Complementary; D009419:Nerve Tissue Proteins; C494212:STX1A protein, human; C494213:Stx1a protein, rat; D050827:Syntaxin 1; C413363:RNF40 protein, human; D044767:Ubiquitin-Protein Ligases; D008025:Ligases