Arginine Methylation of CRTC2 Is Critical in the Transcriptional Control of Hepatic Glucose Metabolism

Han, Hye Sook; Jung, Chang Yun; Yoon, Younju; Choi, Seri; Choi, Dahee; Kang, Geon; Park, Keun Gyu; Kim, Seong-Tae; Koo, Seung Hoi

doi:10.1126/scisignal.2004479

Cited by 33 publications

(25 citation statements)

References 34 publications

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“…Choi et al reported that PRMT1 increases hepatic gluconeogenesis by inhibiting protein kinase B (Akt)-mediated FoxO1 phosphorylation [4]. Han et al reported that PRMT6 promotes fasting-induced hepatic gluconeogenesis via CREB-regulated transcriptional coactivator 2 (CRTC2) methylation [5]. Moreover, we found that PRMT1 and PRMT3 are involved in hepatic lipogenesis [6,7].…”

Section: Introductionmentioning

confidence: 80%

Insulin-induced CARM1 upregulation facilitates hepatocyte proliferation

Yeom

Kim

Park

et al. 2015

Biochemical and Biophysical Research Communications

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Section: Introductionmentioning

confidence: 80%

Insulin-induced CARM1 upregulation facilitates hepatocyte proliferation

Yeom

Kim

Park

et al. 2015

Biochemical and Biophysical Research Communications

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“…Co-IP is a well-established approach for identifying kinase substrates, and has recently been applied to both arginine and lysine methyltransferases 9; 50 . A major advantage of this approach is that it captures enzyme/substrate interactions that may require scaffold proteins or interactions through other biomolecules such as DNA or RNA.…”

Section: Proteome-wide Approaches For Identifying Methyltransferase Amentioning

confidence: 99%

“…Arginine methylation has many critical functions such as in signal transduction 4 , regulation of mRNA splicing and translation 5 , and physiological processes such as glucose homeostasis 6 (reviewed in 7; 8; 9 ). Non-histone lysine methylation regulates pathways including tumor suppression by p53 and signaling by NFκB 10; 11 (reviewed in 12 ).…”

Section: Introductionmentioning

confidence: 99%

Emerging Technologies to Map the Protein Methylome

Carlson

Gozani

2014

Journal of Molecular Biology

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Protein methylation plays an integral role in cellular signaling, most notably by modulating proteins bound at chromatin, and increasingly through regulation of non-histone proteins. One central challenge in understanding how methylation acts in signaling is identifying and measuring protein methylation. This includes locus-specific modification of histones, on individual non-histone proteins, and globally across the proteome. Protein methylation has traditionally been studied using candidate approaches such as methylation-specific antibodies, mapping of post-translational modifications by mass spectrometry, and radioactive labeling to characterize methylation on target proteins. Recent developments have provided new approaches to identify methylated proteins, measure methylation levels, identify substrates of methyltransferase enzymes, and match methylated proteins to methyl-specific reader domains. Methyl-binding protein domains and improved antibodies with broad specificity for methylated proteins are being used to characterize the “protein methylome”. They also have the potential to be used in high-throughput assays for inhibitor screens and drug development. These tools are often coupled to improvements in mass spectrometry to quickly identify methylated residues, and to protein microarrays, where they can be used to screen for methylated proteins. Finally, new chemical biology strategies are being used to probe the function of methyltransferases, demethylases and methyl-binding “reader” domains. These tools are creating a “system-level” understanding of protein methylation, and integrating protein methylation into broader signaling processes.

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“…However, several lines of evidence have shown the importance of type I PRMTs in the liver, as they are responsible for hepatic glucose metabolism. Choi et al (17) and Han et al (18) reported that PRMT1 and PRMT6 regulate hepatic gluconeogenesis. Lee et al (19) also demonstrated an increased ADMA plasma concentration and decreased hepatic PRMT1 expression in diabetic mice (db/db), suggesting that PRMTs play an important role in the onset of diabetes in the liver.…”

mentioning

confidence: 99%

PRMT3 Regulates Hepatic Lipogenesis Through Direct Interaction With LXRα

Kim

Park

Lim³

et al. 2014

Diabetes

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Arginine methylation is responsible for diverse biological functions and is mediated by protein arginine methyltransferases (PRMTs). Nonalcoholic fatty liver disease (NAFLD) is accompanied by excessive hepatic lipogenesis via liver X receptor α (LXRα). Thus we examined the pathophysiological role of PRMTs in NAFLD and their relationship with LXRα. In this study, palmitic acid (PA) treatment increased PRMT3, which is correlated with the elevation of hepatic lipogenic proteins. The expression of lipogenic proteins was increased by PRMT3 overexpression, but decreased by PRMT3 silencing and use of the PRMT3 knockout (KO) mouse embryonic fibroblast cell line. PRMT3 also increased the transcriptional activity of LXRα by directly binding with LXRα in a methylation-independent manner. In addition, PA treatment translocated PRMT3 to the nucleus. In animal models, a high-fat diet increased the LXRα and PRMT3 expressions and binding, which was not observed in LXRα KO mice. Furthermore, increased PRMT3 expression and its binding with LXRα were observed in NAFLD patients. Taken together, LXRα and PRMT3 expression was increased in cellular and mouse models of NAFLD and human patients, and PRMT3 translocated into the nucleus bound with LXRα as a transcriptional cofactor, which induced lipogenesis. In conclusion, PRMT3 translocation by PA is coupled to the binding of LXRα, which is responsible for the onset of fatty liver.

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Arginine Methylation of CRTC2 Is Critical in the Transcriptional Control of Hepatic Glucose Metabolism

Cited by 33 publications

References 34 publications

Insulin-induced CARM1 upregulation facilitates hepatocyte proliferation

Insulin-induced CARM1 upregulation facilitates hepatocyte proliferation

Emerging Technologies to Map the Protein Methylome

PRMT3 Regulates Hepatic Lipogenesis Through Direct Interaction With LXRα

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