File Download

  • Find it @ UNIST can give you direct access to the published full text of this article. (UNISTARs only)
Related Researcher

박태은

Park, Tae-Eun
Micro Tissue Engineering & Nanomedicine Lab.
Read More

Views & Downloads

Detailed Information

Cited time in webofscience Cited time in scopus
Metadata Downloads

PPM1A Controls Diabetic Gene Programming through Directly Dephosphorylating PPARγ at Ser273

Author(s)
Khim, Keon WooChoi, Sun SilJang, Hyun-JunLee, Yo HanLee, EujinHyun, Ji-MinEom, Hye-JinYoon, SoraChoi, Jeong-WonPark, Tae-EunNam, DouguChoi, Jang Hyun
Issued Date
2020-02
DOI
10.3390/cells9020343
URI
https://scholarworks.unist.ac.kr/handle/201301/31145
Fulltext
https://www.mdpi.com/2073-4409/9/2/343
Citation
CELLS, v.9, no.2, pp.343
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.
Publisher
MDPI
ISSN
2073-4409
Keyword (Author)
obesityinsulin sensitivityPPM1APPAR gamma S273 phosphorylationdiabetic gene reprogramming
Keyword
ACTIVATED-RECEPTOR-GAMMAADIPOSE-TISSUE INFLAMMATIONINSULIN-RESISTANCEOBESITYPHOSPHATASEMAGNESIUMADIPOGENESISPHOSPHORYLATIONLIGANDTRANSCRIPTION

qrcode

Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.