Protein farnesylation in mammalian cells: effects of farnesyltransferase inhibitors on cancer cells.
Protein farnesylation, catalyzed by protein farnesyltransferase, plays important roles in the membrane association and protein-protein interaction of a number of eukaryotic proteins. Recent development of farnesyltransferase inhibitors (FTIs) has led to further insight into the biological significance of farnesylation in cancer cells. A number of reports point to the dramatic effects FTIs exert on cancer cells. In addition to inhibiting anchorage-independent growth, FTIs cause changes in the cell cycle either at the G1/S or at the G2/M phase. Furthermore, induction of apoptosis by FTIs has been reported. FTIs also affects the actin cytoskeleton and cell morphology. This review summarizes these reports and discusses implications for farnesylated proteins responsible for these FTI effects.
Tamanoi
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Department of Microbiology and Molecular Genetics, Jonsson Comprehensive Cancer Center, University of California Los Angeles, 90095-1489, USA. fuyut@microbio.ucla.edu
Gau
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Jiang
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Edamatsu
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Kato-Stankiewicz
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D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D048429:Cell Size; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D051231:Farnesyltranstransferase; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D017368:Protein Prenylation; D022502:Stress Fibers / Q000378:metabolism; D014407:Tumor Cells, Cultured; D018631:ras Proteins / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D000970:Antineoplastic Agents; D002868:Chromosomal Proteins, Non-Histone; D004791:Enzyme Inhibitors; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase; D018631:ras Proteins; D020741:rho GTP-Binding Proteins