PPM1A Controls Diabetic Gene Programming through Directly Dephosphorylating PPARγ at Ser273

Cited 0 times inthomson ciCited 0 times inthomson ci
Title
PPM1A Controls Diabetic Gene Programming through Directly Dephosphorylating PPARγ at Ser273
Author
Khim, Keon WooChoi, Sun SilJang, Hyun-JunLee, Yo HanLee, EujinHyun, Ji-MinEom, Hye-JinYoon, SoraChoi, Jeong-WonPark, Tae-EunNam, DouguChoi, Jang Hyun
Issue Date
2020-02
Publisher
MDPI
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.
URI
https://scholarworks.unist.ac.kr/handle/201301/31145
URL
https://www.mdpi.com/2073-4409/9/2/343
DOI
10.3390/cells9020343
ISSN
2073-4409
Appears in Collections:
SLS_Journal Papers
Files in This Item:
000521944900084.pdf Download

find_unist can give you direct access to the published full text of this article. (UNISTARs only)

Show full item record

qrcode

  • mendeley

    citeulike

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

MENU