Meta-Biol

• Pathways

RAS proteins undergo C-terminal carboxymethylation by isoprenylcysteine methyltransferase (ICMT) (Yang et al, 2011; Dharmaiah et al, 2016; reviewed in Gysin et al, 2011; Ahearn et al, 2018). LIke prenylation, methylation is required for plasma membrane localization and function of RAS proteins, and disruption of ICMT or interference with the methylation reaction inhibits cell growth and KRAS-dependent transformation (Chiu et al, 2004; Michaelson et al, 2005; Bergo et al, 2004; Wahlstrom et al, 2008; Winter-Vann et al, 2003). Consistent with this, a number of small molecule inhibitors of ICMT have been shown to decrease tumor proliferation (Wang et al, 2009; Manu et al, 2017; Sun et al, 2016).