Post-prenylation-processing enzymes as new targets in oncogenesis.
RAS and many other oncogenic proteins undergo a complex series of post-translational modifications that are initiated by the addition of an isoprenoid lipid through a process known as prenylation. Following prenylation, these proteins usually undergo endoproteolytic processing by the RCE1 protease and then carboxyl methylation by a unique methyltransferase known as isoprenylcysteine carboxyl methyltransferase (ICMT). Although inhibitors that have been designed to target the prenylation step are now in advanced-stage clinical trials, their utility and efficacy seem to be limited. Recent findings, however, indicate that the inhibition of these post-prenylation-processing steps--particularly that of ICMT-catalysed methylation--might provide a better approach to the control of cancer-cell proliferation.
Winter-Vann
Ann M
AM
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Casey
Patrick J
PJ
D019883:Alkyl and Aryl Transferases / Q000378:metabolism; D000818:Animals; D049109:Cell Proliferation; D010450:Endopeptidases / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000209:etiology*; D011496:Protein Methyltransferases / Q000378:metabolism; D017368:Protein Prenylation; D011499:Protein Processing, Post-Translational; D018631:ras Proteins / Q000378:metabolism*
D011496:Protein Methyltransferases; C056501:protein-S-isoprenylcysteine O-methyltransferase; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; C064911:p21(ras) farnesyl-protein transferase; D010450:Endopeptidases; C491326:RCE1 protein, human; D018631:ras Proteins