PPM1A Controls Diabetic Gene Programming through Directly Dephosphorylating PPARγ at Ser273

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dc.contributor.author Khim, Keon Woo ko
dc.contributor.author Choi, Sun Sil ko
dc.contributor.author Jang, Hyun-Jun ko
dc.contributor.author Lee, Yo Han ko
dc.contributor.author Lee, Eujin ko
dc.contributor.author Hyun, Ji-Min ko
dc.contributor.author Eom, Hye-Jin ko
dc.contributor.author Yoon, Sora ko
dc.contributor.author Choi, Jeong-Won ko
dc.contributor.author Park, Tae-Eun ko
dc.contributor.author Nam, Dougu ko
dc.contributor.author Choi, Jang Hyun ko
dc.date.available 2020-02-13T08:41:42Z -
dc.date.created 2020-02-03 ko
dc.date.issued 2020-02 ko
dc.identifier.citation CELLS, v.9, no.2, pp.343 ko
dc.identifier.issn 2073-4409 ko
dc.identifier.uri https://scholarworks.unist.ac.kr/handle/201301/31145 -
dc.description.abstract Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a master regulator of adipose tissue biology. In obesity, phosphorylation of PPAR gamma at Ser273 (pSer273) by cyclin-dependent kinase 5 (CDK5)/extracellular signal-regulated kinase (ERK) orchestrates diabetic gene reprogramming via dysregulation of specific gene expression. Although many recent studies have focused on the development of non-classical agonist drugs that inhibit the phosphorylation of PPAR gamma at Ser273, the molecular mechanism of PPAR gamma dephosphorylation at Ser273 is not well characterized. Here, we report that protein phosphatase Mg2+/Mn2+-dependent 1A (PPM1A) is a novel PPAR gamma phosphatase that directly dephosphorylates Ser273 and restores diabetic gene expression which is dysregulated by pSer273. The expression of PPM1A significantly decreases in two models of insulin resistance: diet-induced obese (DIO) mice and db/db mice, in which it negatively correlates with pSer273. Transcriptomic analysis using microarray and genotype-tissue expression (GTEx) data in humans shows positive correlations between PPM1A and most of the genes that are dysregulated by pSer273. These findings suggest that PPM1A dephosphorylates PPAR gamma at Ser273 and represents a potential target for the treatment of obesity-linked metabolic disorders. ko
dc.language 영어 ko
dc.publisher MDPI ko
dc.title PPM1A Controls Diabetic Gene Programming through Directly Dephosphorylating PPARγ at Ser273 ko
dc.type ARTICLE ko
dc.identifier.wosid 000521944900084 ko
dc.type.rims ART ko
dc.identifier.doi 10.3390/cells9020343 ko
dc.identifier.url https://www.mdpi.com/2073-4409/9/2/343 ko
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