ICMT

ICMT inhibitors block isoprenylcysteine carboxyl methyltransferase, the last enzyme of protein prenyl processing. Many signaling proteins, including Ras GTPases, end in a cysteine-aliphatic-aliphatic-any amino acid (CAAX) motif that is prenylated, trimmed and then methylated. Methylation of the prenylated cysteine helps these proteins associate with cell membranes. In 1998 the mammalian methyltransferase was localized to the endoplasmic reticulum. Cysmethynil, reported in 2005 as a small-molecule ICMT inhibitor, mislocalized Ras and impaired epidermal growth factor signaling in cancer cells. UCM-1336, POP-3MB and ICMT-IN-1 are further inhibitors used to study Ras membrane targeting and cell growth.