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Science. 2004 Oct 1;306(5693):117-20.

Ubistatins inhibit proteasome-dependent degradation by binding the ubiquitin chain.

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1
Department of Biology, Howard Hughes Medical Institute (HHMI), California Institute of Technology, Pasadena, CA 91125, USA.

Erratum in

  • Science. 2008 May 16;320(5878):874.

Abstract

To identify previously unknown small molecules that inhibit cell cycle machinery, we performed a chemical genetic screen in Xenopus extracts. One class of inhibitors, termed ubistatins, blocked cell cycle progression by inhibiting cyclin B proteolysis and inhibited degradation of ubiquitinated Sic1 by purified proteasomes. Ubistatins blocked the binding of ubiquitinated substrates to the proteasome by targeting the ubiquitin-ubiquitin interface of Lys(48)-linked chains. The same interface is recognized by ubiquitin-chain receptors of the proteasome, indicating that ubistatins act by disrupting a critical protein-protein interaction in the ubiquitin-proteasome system.

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PMID:
15459393
DOI:
10.1126/science.1100946
[Indexed for MEDLINE]
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