Context of Multiubiquitin Chain Attachment Influences the Rate of Sic1 Degradation

• Autores: Raymond J. Deshaies, Matthew D. Petroski
• Localización: Molecular cell, ISSN 1097-2765, Vol. 11, Nº 6, 2003, pág. 1435
• Idioma: inglés
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• Resumen

  • The ubiquitin-dependent targeting of proteins to the proteasome is an essential mechanism for regulating eukaryotic protein stability. Here we define the minimal signal for the degradation of the S phase CDK inhibitor Sic1. Of 20 lysines scattered throughout Sic1, 6 N-terminal lysines serve as major ubiquitination sites. Sic1 lacking these lysines (K0N) is stable in vivo, but readdition of any one restores turnover. Nevertheless, ubiquitin chains attached at different N-terminal lysines specify degradation in vitro at markedly different rates. Moreover, although K0N can be ubiquitinated by SCFCdc4/Cdc34 in vitro in the absence (but not in the presence) of S-CDK, it is degraded slowly. Our results reveal that a single multiubiquitin chain can sustain a physiological turnover rate, but that chain position plays an unexpectedly significant role in the rate of proteasomal proteolysis.