CARM1 (coactivator-associated arginine methyltransferase 1), also known as PRMT4 (protein arginine N-methyltransferase 4), is an
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
() encoded by the gene found in human beings, as well as many other mammals.
It has a polypeptide (L) chain type that is 348 residues long, and is made up of alpha helices and beta sheets.
Its main function includes catalyzing the transfer of a methyl group from
S-Adenosyl methionine
''S''-Adenosyl methionine (SAM), also known under the commercial names of SAMe, SAM-e, or AdoMet, is a common cosubstrate involved in methyl group transfers, transsulfuration, and aminopropylation. Although these anabolic reactions occur throug ...
to the side chain nitrogens of
arginine residues within proteins to form methylated arginine derivatives and
S-Adenosyl-L-homocysteine.
CARM1 is a secondary
coactivator
A coactivator is a type of transcriptional coregulator that binds to an activator (a transcription factor) to increase the rate of transcription of a gene or set of genes. The activator contains a DNA binding domain that binds either to a DNA ...
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.
Clinical significance
CARM1 plays an important role in androgen receptors and may play a role in prostate cancer progression.
CARM1 exerts both oncogenic and tumor-suppressive functions. In breast cancer, CARM1 methylates
chromatin remodeling
Chromatin remodeling is the dynamic modification of chromatin architecture to allow access of condensed genomic DNA to the regulatory transcription machinery proteins, and thereby control gene expression. Such remodeling is principally carried out ...
factor BAF155 to enhance tumor progression and metastasis. In
pancreatic cancer
Pancreatic cancer arises when cell (biology), cells in the pancreas, a glandular organ behind the stomach, begin to multiply out of control and form a Neoplasm, mass. These cancerous cells have the malignant, ability to invade other parts of t ...
, CARM1 methylates and inhibits
MDH1
Malate dehydrogenase, cytoplasmic also known as malate dehydrogenase 1 is an enzyme that in humans is encoded by the MDH1 gene.
Function
Malate dehydrogenase catalyzes the reversible oxidation of malate to oxaloacetate, utilizing the NAD/NADH c ...
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
Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily Detoxification, detoxify the reactive intermediates or to repair the resulting damage. Disturbances ...
, thereby suppressing cell proliferation and colony formation.
See also
*
histone-arginine N-methyltransferase
External links
*
*
References
Transcription coregulators
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