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Protein prenylation: from discovery to prospects for cancer treatment
M H Gelb1, J D Scholten, J S Sebolt-Leopold
1Department of Chemistry, Box 351700, University of Washington, Seattle, WA 98195, USA. gelb@chem.washington.edu
Abstract:
A specific set of proteins in eukaryotic cells contain covalently attached carboxy-terminal prenyl groups (15-carbon farnesyl and 20-carbon geranylgeranyl). Many of them are signaling proteins including Ras, heterotrimeric G proteins and Rab proteins. The protein prenyltransferases which attach prenyl groups to proteins have been well characterized, and an X-ray structure is available for protein farnesyltransferase. Inhibitors of protein farnesyltransferase are showing sufficient promise in preclinical trials as anti-cancer drugs to warrant widespread interest in the pharmaceutical industry.