Protein-L-isoaspartate(D-aspartate) O-methyltransferase (PCMT1)

Protein-L-isoaspartate(D-aspartate) O-methyltransferase (PCMT1), also known as PIMT, is a highly conserved enzyme responsible for the repair of age-damaged proteins by recognizing and methylating L-isoaspartyl and D-aspartyl residues. These residues are spontaneous degradation products of L-aspartyl and L-asparaginyl residues, and their accumulation can impair protein structure and function. PCMT1 initiates a repair cycle that converts these abnormal residues back to the normal L-aspartyl form, thereby restoring protein integrity. Beyond its repair role, PCMT1 regulates critical cellular processes such as the stability of the tumor suppressor p53, epithelial-mesenchymal transition (EMT), and the generation of degrons for cereblon-mediated protein degradation. In various cancers, PCMT1 is overexpressed and acts as an oncogene by promoting cell migration, invasion, and resistance to apoptosis, making it a potential therapeutic target. Conversely, its deficiency is linked to severe neurodegeneration and fatal epilepsy, as demonstrated in knockout mouse models, highlighting its essential role in the central nervous system. While no specific drugs targeting PCMT1 are currently in clinical use, small molecule inhibitors and silencing strategies are being explored for cancer therapy. The enzyme's activity is inhibited by S-adenosyl-L-homocysteine and adenosine periodate-oxidized, which serve as important tools in biochemical research.

Other names

Protein L-isoaspartyl methyltransferaseL-isoaspartyl protein carboxyl methyltransferaseProtein L-isoaspartyl/D-aspartyl methyltransferaseProtein-beta-aspartate methyltransferasePIMTPCMT-1

Inhibition of the enzyme's catalytic activity to prevent the repair of damaged proteins in cancer cells, thereby promoting apoptosis and reducing metastasis; or modulation of p53 stability and EMT-related signaling pathways.