Farnesylated proteins and cell cycle progression.
Post-translational modification of proteins by the addition of a farnesyl group is critical for the function of a number of proteins involved in signal transduction. Farnesylation facilitates their membrane association and also promotes protein-protein interaction. Recently, progress has been made in understanding the biological significance of farnesylation. First, effects of farnesyltransferase inhibitors (FTIs) on cancer cells have been examined using a variety of human cancer cells. This study showed that one of the major effects of FTIs is to alter cell cycle progression. Both G0/G1 enrichment and G2/M accumulation were observed depending on the cell line examined. Second, a number of novel farnesylated proteins have been characterized. Of these, Rheb and CENP-E,F are of particular interest. Rheb, a novel member of the Ras superfamily G-proteins, may play a role in the G1 phase of the cell cycle. CENP-E,F are centromere associated motors that play critical roles in mitosis. These results suggest important contributions of farnesylated proteins in the regulation of cell cycle progression.
Tamanoi
F
F
Department of Microbiology, Immunology and Molecular Genetics, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California 90095-1489, USA. fuyut@microbio.ucla.edu
Kato-Stankiewicz
J
J
Jiang
C
C
Machado
I
I
Thapar
N
N
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051231:Farnesyltranstransferase; D016193:G1 Phase / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008840:Microfilament Proteins; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D017368:Protein Prenylation / Q000502:physiology*; D015363:Quinolones / Q000494:pharmacology; D000076205:Ras Homolog Enriched in Brain Protein; D016192:Resting Phase, Cell Cycle / Q000187:drug effects / Q000502:physiology; D014407:Tumor Cells, Cultured
D002868:Chromosomal Proteins, Non-Histone; D004791:Enzyme Inhibitors; D008840:Microfilament Proteins; D009479:Neuropeptides; D015363:Quinolones; C490211:RHEB protein, human; D000076205:Ras Homolog Enriched in Brain Protein; C068688:centromere protein E; C094772:centromere protein F; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase; D020559:Monomeric GTP-Binding Proteins; C402769:tipifarnib