Analysis of the function of GADD34 in cell growth, migration and starvation-stress response

2015 Fiscal Year Final Research Report

• Project/Area Number: 24500852
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied health science
• Research Institution: Nagoya University
• Principal Investigator: Ito Sachiko 名古屋大学, 医学(系)研究科(研究院), 講師 (70447845)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: GADD34 / マクロファージ / オートファジー / アポトーシス / 栄養欠乏 / 創傷治癒 / シグナル伝達 / 炎症

Outline of Final Research Achievements

In this study, we analyzed the function of GADD34 on nutrition starvation-stress responses in macrophages. The deprivation of tyrosine and cysteine (Tyr/Cys) induced the expression of GADD34 in macrophages. LPS stimulation combined with Tyr/Cys-deprivation activated macrophages, then shifted to cell death in late phase of stimulation. A deficiency of GADD34 enhanced cell activation signaling and apoptosis more than that in wild-type macrophages. Further we found that mTOR-S6K signaling was higher in GADD34-deficient macrophages than in wild-type cells. Defective GADD34 reduced LC3-II and autophagosome formation induced by LPS-stimulation and Tyr/Cys-deprivation compared with that in wild-type macrophages. These results indicate that GADD34 enhances autophagy and suppresses apoptosis stimulated by LPS combined with amino acid deprivation through regulation of mTOR signaling pathway in macrophages.

Free Research Field

免疫学