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Protein arginine methylation: an emerging regulator of the cell cycle - PubMed

  • ️Mon Jan 01 2018

Review

Protein arginine methylation: an emerging regulator of the cell cycle

Anita E Raposo et al. Cell Div. 2018.

Abstract

Protein arginine methylation is a common post-translational modification where a methyl group is added onto arginine residues of a protein to alter detection by its binding partners or regulate its activity. It is known to be involved in many biological processes, such as regulation of signal transduction, transcription, facilitation of protein-protein interactions, RNA splicing and transport. The enzymes responsible for arginine methylation, protein arginine methyltransferases (PRMTs), have been shown to methylate or associate with important regulatory proteins of the cell cycle and DNA damage repair pathways, such as cyclin D1, p53, p21 and the retinoblastoma protein. Overexpression of PRMTs resulting in aberrant methylation patterns in cancers often correlates with poor recovery prognosis. This indicates that protein arginine methylation is also an important regulator of the cell cycle, and consequently a target for cancer regulation. The effect of protein arginine methylation on the cell cycle and how this emerging key player of cell cycle regulation may be used in therapeutic strategies for cancer are the focus of this review.

Keywords: Cancer; Cell cycle regulation; DNA repair; Protein arginine methylation; p53.

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Figures

Fig. 1
Fig. 1

Overview of the regulation of the cell cycle. The cell cycle is depicted as a circle where each black arrow represents one phase of the cell cycle. Cells enter the cell cycle into the G1 phase, which is followed by the S phase, G2 phase and then mitosis (M). The cell cycle is regulated by CDKs (purple), their regulatory subunit cyclins (pink), CDK inhibitors such as p21 (light blue), and other regulatory kinases, such as the checkpoint kinases 1 and 2 (Chk1 and Chk2; yellow). The orange lines at the end of G1, G2 and during mitosis indicate cell cycle checkpoints where the cell is monitored for defects during replication and can respond by the p53 (green) pathway or the ATM/R (red) pathway, among others. Yellow circles with “M” indicate proteins known to be methylated on arginine residues and the dark blue circles with “P” indicate phosphorylation of pRB

Fig. 2
Fig. 2

Types of mammalian protein arginine methylation. Arginine residues in proteins can be monomethylated by type I, II and III PRMTs to form MMA, while type I and II PRMTs further methylate to produce ADMA and SDMA residues, respectively. Red arrows indicate known methylation locations in mammalian cells; red circles indicate methyl groups

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