CARM1 (coactivator-associated arginine methyltransferase 1), also known as PRMT4 (protein arginine N-methyltransferase 4), is an enzyme (EC2.1.1.125) encoded by the CARM1 gene found in human beings, as well as many other mammals.[2] It has a polypeptide (L) chain type that is 348 residues long, and is made up of alpha helices and beta sheets.[3] Its main function includes catalyzing the transfer of a methyl group from S-Adenosyl methionine to the side chain nitrogens of arginine residues within proteins to form methylated arginine derivatives and S-Adenosyl-L-homocysteine.[4] CARM1 is a secondary coactivator through its association with p160 family (SRC-1, GRIP1, AIB) of coactivators. It is responsible for moving cells toward the inner cell mass in developing blastocysts.[5]
Clinical significance
CARM1 plays an important role in androgen receptors and may play a role in prostate cancer progression.[6][7]
CARM1 exerts both oncogenic and tumor-suppressive functions. In breast cancer, CARM1 methylates chromatin remodeling factor BAF155 to enhance tumor progression and metastasis.[8] In pancreatic cancer, CARM1 methylates and inhibits MDH1 by disrupting its dimerization, which represses mitochondria respiration and inhibits glutamine utilization. CARM1-mediated MDH1 methylation reduces cellular NADPH level and sensitizes cells to oxidative stress, thereby suppressing cell proliferation and colony formation.[9]
^Chen D, Ma H, Hong H, Koh SS, Huang SM, Schurter BT, Aswad DW, Stallcup MR (1999). "Regulation of transcription by a protein methyltransferase". Science. 284 (5423): 2174–7. doi:10.1126/science.284.5423.2174. PMID10381882.
^Hong H, Kao C, Jeng MH, Eble JN, Koch MO, Gardner TA, Zhang S, Li L, Pan CX, Hu Z, MacLennan GT, Cheng L (2004). "Aberrant expression of CARM1, a transcriptional coactivator of androgen receptor, in the development of prostate carcinoma and androgen-independent status". Cancer. 101 (1): 83–9. doi:10.1002/cncr.20327. PMID15221992. S2CID274474.
^Majumder S, Liu Y, Ford OH, Mohler JL, Whang YE (2006). "Involvement of arginine methyltransferase CARM1 in androgen receptor function and prostate cancer cell viability". Prostate. 66 (12): 1292–301. doi:10.1002/pros.20438. PMID16705743. S2CID23950904.
