A functional proteomics approarch to mechanism of radiation sensitivity.

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461880
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: The University of Tokyo
• Principal Investigator: Enomoto Atsushi 東京大学, 大学院医学系研究科(医学部), 講師 (20323602)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: Proteomics / STK38 / Radiation sensitivity / DNA damage responses

Outline of Final Research Achievements

STK38 (serine/threonine kinase 38), also known as NDR1 (nuclear Dbf2-related 1, is a serine/threonine protein kinase belonging to a subclass of the protein kinase A (PKA)/PKG/PKC-like (AGC) family, which includes cAMP-dependent kinase, protein kinase B, and protein kinase C. Knockdown of STK38 enhacnes cellular radio-sensitivity. However, its substrates and downstream signaling pathways remain to be determined. The fuction proteomics approarch revealved that STK38 endogenouly interact with CDC25A and that STK38 directly regulates CDC25A’s stability by phosphorylating Ser-76.Moreover, the STK38/CDC25A signaling module is demonstrated to be required to regulate the DNA-damage-induced G2/M checkpoint. Together, the results suggest thatthe STK38 knockdown-mediated radiosensitization may be due, at least in part, to impaired DNA damage-induced G2 arrest resulting from defective CDC25A degradation.

Free Research Field

放射線生物学