Icmt (Isoprenylcysteine Carboxyl Methyltransferase)
Isoprenylcysteine carboxyl methyltransferase (Icmt) is the only known prenylcysteine protein-dependent methyltransferase and plays a critical role in the posttranslational modification of prenylated proteins (Bergo et al. 2000). The Icmt ortholog from Saccharomyces cerevisiae, STE14p, was the first prenylcysteine carboxyl methyltransferase to be cloned and sequenced, and it is considered the founding member of this eukaryote protein methyltransferase family (Anderson et al. 2005). STE14p was originally recognized in a screen of mutant yeast, deficient of STE14, which rendered the yeast sterile due to their failure to methylate the mating pheromone a-factor, a protein crucial for fertility. STE14p is a 26 kDa integral membrane protein with multiple transmembrane (TM)-spanning domains and is localized to the endoplasmic reticulum (ER) (Romano and Michaelis 2001). Human Icmt cDNA possess notable homology...
KeywordsPrenylated Protein CaaX Motif Metastatic Breast Cancer Cell Line FTase Inhibitor Classical Competitive Inhibitor
- Cushman I, Cushman SM, Potter PM, Casey PJ. Control of RhoA methylation by carboxylesterase I. J Biol Chem. 2013;288(26):19177–83.Google Scholar
- Kowluru A, Seavey SE, Li G, Sorenson RL, Weinhaus AJ, Nesher R, et al. Glucose- and GTP-dependent stimulation of the carboxyl methylation of CDC42 in rodent and human pancreatic islets and pure beta cells. Evidence for an essential role of GTP-binding proteins in nutrient-induced insulin secretion. J Clin Invest. 1996;98(2):540–55.CrossRefPubMedPubMedCentralGoogle Scholar
- Majmudar JD, Hodges-Loaiza HB, Hahne K, Donelson JL, Song J, Shrestha L, Harrison ML, Hrycyna CA, Gibbs RA. Amide-modified prenylcysteine based Icmt inhibitors: structure-activity relationships, kinetic analysis and cellular characterization. Bioorg Med Chem. 2012;20(1):283–95.CrossRefPubMedGoogle Scholar