Fighting cancer by disrupting C-terminal methylation of signaling proteins
J. Clin. Invest. Steven Clarke, et al. 113:513 doi:10.1172/JCI21059 [Go to this article.]

Figure 1
Modification pathway of proteins for isoprenylation/methylation and effects of inhibitors of each enzymatic step. Proteins ending with the CAAX motif undergo farnesylation in the cytosol. Subsequent removal of three C-terminal amino acids and C-terminal methylation are catalyzed by the endoplasmic reticulum–bound enzymes Rce1 and Icmt, respectively. Inhibition of Icmt leads to rapid turnover of RhoA, increase of p21^Cip1, and cell cycle block. R115777, SCH66336, and BMS214662 are farnesyltransferase (Ftase) inhibitors, while farnesylcysteine and AdoHcy inhibit Icmt.