Protein Arginine Methyltransferase 1: A Multi-Purpose Player in the Development of Cancer and Metabolic Disease

Abstract

Protein arginine methyltransferase 1 (PRMT1) is the main PRMT family member involved in the formation of monomethylarginine and asymmetric dimethylarginine on its protein substrates. Many protein substrates of PRMT1 are key mediators of cell proliferation and oncogenesis. As such, the function of PRMT1 has been most prominently investigated in the context of cancer development. However, recent in vitro and in vivo studies have highlighted that PRMT1 may also promote metabolic disorders. With the current review, we aim to present an in-depth overview of how PRMT1 influences epigenetic modulation, transcriptional regulation, DNA damage repair, and signal transduction in cancer. Furthermore, we summarize the current knowledge regarding the role of PRMT1 in metabolic reprogramming, lipid metabolism, and glucose metabolism and describe the association of PRMT1 with numerous metabolic pathologies such as obesity, liver disease, and type 2 diabetes. It has become apparent that inhibiting the function of PRMT1 will likely serve as the most beneficial therapeutic approach, since several PRMT1 inhibitors have already been shown to exert positive effects on both cancer and metabolic disease in preclinical settings. However, pharmacological PRMT1 inhibition has not yet been shown to be therapeutically effective in clinical studies.

Keywords: PRMT1; cancer; liver disease; metabolism; obesity; protein arginine methyltransferase; type 2 diabetes.

Figure 1

The three types of protein arginine methyltransferases. Each PRMT catalyzes the formation of MMA on one of the terminal guanidine nitrogen atoms of the arginine in target proteins. Type I PRMTs subsequently convert MMA into ADMA, whereas type II PRMTs generate SDMA. Type III PRMTs are only able to produce MMA.

Figure 2

The influence of PRMT1 on various cellular processes in cancer. PRMT1 manages H4R3, transcriptional regulation, DNA damage repair, and signal transduction by methylating a wide variety of proteins. Dysregulation of these processes by PRMT1 has been detected in many types of cancer.

Figure 3

Metabolic routes affected by PRMT1. PRMT1 dysfunction has been detected in metabolic reprogramming, lipid metabolism, and glucose metabolism, which is associated with numerous pathologies such as obesity, liver disease, and type 2 diabetes.