Oncotarget

Reviews:

Protein arginine methyltransferase 5 (PRMT5) dysregulation in cancer

Harshita Shailesh _, Zain Z. Zakaria, Robert Baiocchi and Saïd Sif

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Oncotarget. 2018; 9:36705-36718. https://doi.org/10.18632/oncotarget.26404

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Abstract

Harshita Shailesh1, Zain Z. Zakaria1, Robert Baiocchi2 and Saïd Sif1

1Department of Biological and Environmental Sciences, College of Arts and Sciences, Qatar University, Doha, Qatar

2Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA

Correspondence to:

Saïd Sif, email: ssif@qu.edu.qa

Keywords: PRMT5; histone arginine methylation; tumor suppressors; proliferative signaling; metabolic dysregulation

Received: August 06, 2018     Accepted: November 16, 2018     Published: November 30, 2018

ABSTRACT

Protein arginine methyltransferases (PRMTs) are known for their ability to catalyze methylation of specific arginine residues in a wide variety of cellular proteins, which are involved in a plethora of processes including signal transduction, transcription, and more recently DNA recombination. All members of the PRMT family can be grouped into three main classes depending on the type of methylation they catalyze. Type I PRMTs induce monomethylation and asymmetric dimethylation, while type II PRMTs catalyze monomethylation and symmetric dimethylation of specific arginine residues. In contrast, type III PRMTs carry out only monomethylation of arginine residues. In this review, we will focus on PRMT5, a type II PRMT essential for viability and normal development, which has been shown to be overexpressed in a wide variety of cancer cell types, owing it to the crucial role it plays in controlling key growth regulatory pathways. Furthermore, the role of PRMT5 in regulating expression and stability of key transcription factors that control normal stem cell function as well as cancer stem cell renewal will be discussed. We will review recent work that shows that through its ability to methylate various cellular proteins, PRMT5 functions as a master epigenetic regulator essential for growth and development, and we will highlight studies that have examined its dysregulation and the effects of its inhibition on cancer cell growth.


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