Protein prenylation: from discovery to prospects for cancer treatment.
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.
Gelb
M H
MH
Department of Chemistry, Box 351700, University of Washington, Seattle, WA 98195, USA. gelb@chem.washington.edu
Scholten
J D
JD
Sebolt-Leopold
J S
JS
D019883:Alkyl and Aryl Transferases / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D017368:Protein Prenylation
D000970:Antineoplastic Agents; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase