CARM1

Official Full Name

coactivator associated arginine methyltransferase 1

Organism

Homo sapiens

GeneID

10498

Background

This gene belongs to the protein arginine methyltransferase (PRMT) family. The encoded enzyme catalyzes the methylation of guanidino nitrogens of arginyl residues of proteins. The enzyme acts specifically on histones and other chromatin-associated proteins and is involved in regulation of gene expression. The enzyme may act in association with other proteins or within multi-protein complexes and may play a role in cell type-specific functions and cell lineage specification. A related pseudogene is located on chromosome 9. [provided by RefSeq, Aug 2013]

Synonyms

PRMT4;

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Detailed Information

Recent Research Progress

The enzyme co-activator-associated arginine methyltransferase 1 (CARM1) has a wide range of roles in embryonic development and cell differentiation. CARM1, also known as protein arginine methyltransferase 4 (PRMT4), is a type I arginine methyltransferase enzyme, which adds asymmetric dimethylation to arginine residues in histones, with specificity for H3R17 and H3R26, as well as an ever increasing number of other protein substrates. These substrates include the transcription factor RUNX1, co-activators such as p300, CBP and AIB1, as well as chromatin regulatory proteins including members of the SWI/SNF, COMPASS and Mediator complexes. CARM1 also methylates RNA binding proteins such as PABP1 and various splicing factors, including CA150, SAP49, SmB and U1C. Through these modifications and others, CARM1 regulates key cellular processes such as RNA splicing and autophagy. Emerging evidence suggests that CARM1 acts as an oncogene in human cancer.

CARM1 and OS

Osteosarcoma (OS) is a malignant bone tumor that often occurs in the area around the knee and poses a threat to the health of adolescents. Recent studies have found that overexpression of CARM1 was associated with the Enneking stage of OS. The knockdown of CARM1 expression reduces proliferation and affects the cell cycle in OS cell lines. Most importantly, the knockdown of CARM1 down-regulated the activity of GSK3β and decreased the expression of β-catenin and cyclinD1. Therefore, CARM1 may affect Wnt signaling to promote OS proliferation. It may be a new target for OS treatment.

CARM1 and PDAC

Pancreatic ductal adenocarcinoma (PDAC) cells rely on an unconventional metabolic pathway catalyzed by aspartate aminotransferase, malate dehydrogenase 1 (MDH1) and malic enzyme 1 to re-attach glutamine metabolism and support nicotinamide adenine dinucleotide phosphate (NADPH) production. Recently, studies have found that methylation of arginine 248 (R248) negatively regulates MDH1. CARM1 methylates and inhibits MDH1 by disrupting its dimerization. Knockout MDH1 inhibits mitochondrial respiration and inhibits glutamine metabolism, making PDAC cells susceptible to oxidative stress and inhibiting cell proliferation. At the same time, re-expression of wild-type MDH1, but not its methylation mimetic mutants, protects cells from oxidative damage and restores cell growth and clonogenic activity. Importantly, in clinical PDAC samples, MDH1 is hypomethylated at R248. Studies have shown that arginine methylation of MDH1 by CARM1 regulates cellular redox homeostasis and suppresses glutamine metabolism of pancreatic cancer.

CARM1 and AML

Loss of CARM1 has been reported to have little effect on normal hematopoiesis. Strikingly, knockout of CARM1 abolished the initiation and maintenance of acute myeloid leukemia (AML) driven by oncogenic transcription factors. Knockdown of CARM1 impairs cell cycle progression, promotes bone marrow differentiation, and ultimately induces apoptosis. The efficacy of CARM1 inhibition in vitro and in vivo in leukemia cells was verified using a selective small molecule inhibitor of CARM1. The results showed that the AML mouse model is highly sensitive to CARM1 inhibition in vivo, showing a significant decrease in AML cell growth and an increase in survival. These results suggest that targeting CARM1 may be an effective therapeutic strategy for AML.

In addition, high levels of CARM1 expression have been observed in other cancer types, including breast, colon and liver cancers, but the mechanisms involved in cancer development are unclear. Therefore, clinically applicable therapeutic strategies based on CARM1 expression in cancer are still to be explored.

References:

Li SJ, et al. The Overexpression of CARM1 Promotes Human Osteosarcoma Cell Proliferation through the pGSK3β/β-Catenin/cyclinD1 Signaling Pathway. International Journal of Biological Sciences, 2017, 13(8): 976-984.
Wang YP, et al. Arginine Methylation of MDH1 by CARM1 Inhibits Glutamine Metabolism and Suppresses Pancreatic Cancer. Molecular Cell, 2016, 64: 673–687
Sarah M, et al. CARM1 Is Essential for Myeloid Leukemogenesis but Dispensable for Normal Hematopoiesis. Cancer Cell, 2018, 33: 1111–1127
Wang L, et al. MED12 methylation by CARM1 sensitizes human breast cancer cells to chemotherapy drugs. Science Advances, 2015, 1(9)
Zheng L, et al. miR-195 enhances the radiosensitivity of colorectal cancer cells by suppressing CARM1. OncoTargets and Therapy, 2017, 10: 1027–1038
Fan X, et al. CARF activates beta-catenin/TCF signaling in the hepatocellular carcinoma. Oncotarget, 2016, 7(49): 80404-80414
Yeom Chul-gon, et al. Insulin-induced CARM1 upregulation facilitates hepatocyte proliferation. Biochemical and Biophysical Research Communications, 2015, 461: 568e574

Quick Inquiry

Interested in learning more?

Contact us today for a free consultation with the scientific team and discover how Creative Biogene can be a valuable resource and partner for your organization.

Request a quote today!

Inquiry