Dephosphorylation of SREBP1c by protein phosphatase PPM1L

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K09016
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Tohoku University
• Principal Investigator: Kobayashi Takayasu 東北大学, 動物・遺伝子実験支援センター, 准教授 (10221970)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: protein phosphatase

Outline of Final Research Achievements

Obesity is a significant risk factor for diabetes and cardiovascular diseases. In an earlier study using quantitative trait loci (QTL) analysis in mice, protein phosphatase PPM1L was identified as a gene related to obesity and other metabolic syndrome traits (Chen et al., 2008), but the underlying mechanism remains unclear. In this study, Thr402 of SREBP1c, which is involved in the ubiquitin-dependent degradation of SREBP, was efficiently dephosphorylated by PPM1L in vitro. In addition, PPM1L KO cells showed enhanced attachment to the culture dish. This is probably due to the enhanced expression of integrins. In PPM1L KO cells, phosphorylation of Smad2 was enhanced, suggesting that PPM1L is involved in regulating TGFβ/Smad pathway.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

肥満は、糖尿病や脂質異常症、高血圧症、心血管疾患などの多くの疾患の原因となるため、その予防は健康な生活を送る上で重要である。本研究では、脂質代謝に関わる重要な因子であるSREBP1c の調節にタンパク質脱リン酸化酵素であるPPM1Lが関わる可能性を示すことができ、生活習慣病の予防に資することが期待できる。