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Ubistatins inhibit proteasome-dependent degradation by binding the ubiquitin chain SCIENCE Verma, R., Peters, N. R., D'onofrio, M., Tochtrop, G. P., Sakamoto, K. M., Varadan, R., Zhang, M. S., Coffino, P., Fushman, D., Deshaies, R. J., King, R. W. 2004; 306 (5693): 117-120

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.

View details for Web of Science ID 000224304000050

View details for PubMedID 15459393