Post-prenylation-processing enzymes as new targets in oncogenesis

Nat Rev Cancer. 2005 May;5(5):405-12. doi: 10.1038/nrc1612.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Alkyl and Aryl Transferases / metabolism
  • Animals
  • Cell Proliferation
  • Endopeptidases / metabolism
  • Humans
  • Neoplasms / etiology*
  • Protein Methyltransferases / metabolism
  • Protein Prenylation*
  • Protein Processing, Post-Translational
  • ras Proteins / metabolism*

Substances

  • Protein Methyltransferases
  • protein-S-isoprenylcysteine O-methyltransferase
  • Alkyl and Aryl Transferases
  • geranylgeranyltransferase type-I
  • p21(ras) farnesyl-protein transferase
  • Endopeptidases
  • RCE1 protein, human
  • ras Proteins