Phospho-signaling pathway dependent on an ATM kinase activated by oxidative stress

Research Project

Project/Area Number	25871242
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	General medical chemistry Risk sciences of radiation and chemicals
Research Institution	独立行政法人医薬基盤研究所
Principal Investigator	HASHIGUCHI Kazunari 独立行政法人医薬基盤研究所, 創薬基盤研究部, 特任研究員 (80400414)
Project Period (FY)	2013-04-01 – 2015-03-31
Project Status	Completed (Fiscal Year 2014)
Budget Amount *help	¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000) Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords	ATM / キナーゼ / リン酸化 / シグナル伝達 / 活性酸素 / 酸化ストレス
Outline of Final Research Achievements	Although an ATM has been supposed to be a kinase that is activated by DNA damage response, recent work revealed that it is also activated by oxidative stress thorough distinct regulation. In this study, I attempt to figure out ATM-dependent phospho-signaling pathway in these two activation systems. For detection of substrates phosphorylated by ATM, several anti-phospho ATM substrate antibodies are used in Western blot analyses. After giving two kinds of cellular stresses, wild-type cells show different substrate pattern even if ATM-deficient cells has same, indicating that detected substrates are specific to ATM and different cellular signals give different substrates which are in ATM-dependent pathway. Further analysis, such as phospho-proteome analysis of ATM substrates, will give valuable information in phosphor-signaling pathways response to various cellular stresses.