Protein Arginine Methylation: from Enigmatic Functions to Therapeutic Targeting

Overview

Journal Nat Rev Drug Discov

Specialty Pharmacology

Date 2021 Mar 20

PMID 33742187

Citations 142

Authors

Qin Wu

Matthieu Schapira

Cheryl H Arrowsmith

Dalia Barsyte-Lovejoy

Affiliations

Soon will be listed here.

Abstract

Protein arginine methyltransferases (PRMTs) are emerging as attractive therapeutic targets. PRMTs regulate transcription, splicing, RNA biology, the DNA damage response and cell metabolism; these fundamental processes are altered in many diseases. Mechanistically understanding how these enzymes fuel and sustain cancer cells, especially in specific metabolic contexts or in the presence of certain mutations, has provided the rationale for targeting them in oncology. Ongoing inhibitor development, facilitated by structural biology, has generated tool compounds for the majority of PRMTs and enabled clinical programmes for the most advanced oncology targets, PRMT1 and PRMT5. In-depth mechanistic investigations using genetic and chemical tools continue to delineate the roles of PRMTs in regulating immune cells and cancer cells, and cardiovascular and neuronal function, and determine which pathways involving PRMTs could be synergistically targeted in combination therapies for cancer. This research is enhancing our knowledge of the complex functions of arginine methylation, will guide future clinical development and could identify new clinical indications.

Citing Articles

PRMT5-mediated arginine methylation stabilizes GPX4 to suppress ferroptosis in cancer.

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Targeting the PRMT1-cGAS-STING signaling pathway to enhance the anti-tumor therapeutic efficacy.

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Implication of protein post translational modifications in gastric cancer.

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Opto-Epigenetic Regulation of Histone Arginine Asymmetric Dimethylation via Type I Protein Arginine Methyltransferase Inhibition.

Xu S, Long K, Wang T, Zhu Y, Zhang Y, Wang W J Med Chem. 2025; 68(4):4373-4381.

PMID: 39961800 PMC: 11873949. DOI: 10.1021/acs.jmedchem.4c02199.

Arginine: at the crossroads of nitrogen metabolism.

Fung T, Ryu K, Thompson C EMBO J. 2025; 44(5):1275-1293.

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