Journal
NATURE REVIEWS CANCER
Volume 5, Issue 5, Pages 405-412Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nrc1612
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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.
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