Isoprenylcysteine carboxyl methyltransferase (ICMT) (ICMT)

Isoprenylcysteine carboxyl methyltransferase (ICMT) is an integral membrane protein of the endoplasmic reticulum that catalyzes the final step in the post-translational processing of CAAX motif proteins, such as RAS GTPases and lamins [1][2]. It facilitates the S-adenosyl-L-methionine-dependent methylation of the C-terminal isoprenylcysteine, a step essential for the proper membrane targeting and functional activation of these proteins [2][3]. In the context of oncology, ICMT is a significant therapeutic target because its inhibition disrupts the membrane localization of oncogenic RAS, thereby suppressing proliferative signaling pathways [4][5]. Furthermore, ICMT inhibition has shown promise in treating Hutchinson-Gilford Progeria Syndrome (HGPS) by ameliorating the toxic effects of progerin [6]. Therapeutic strategies include small molecule inhibitors like cysmethynil and potential RNA-targeted therapies aimed at reducing ICMT mRNA levels to decrease enzyme production [5][7].

Other names

Protein-S-isoprenylcysteine O-methyltransferasePrenylcysteine carboxyl methyltransferasePCCMTSTE14 homologH-ICMT

Inhibition of the enzymatic methylation of the C-terminal isoprenylcysteine of CAAX proteins, or degradation of the encoding mRNA to prevent enzyme synthesis.