Analysis of protein degradation promoting mechanism derived from abnormal mRNA

2016 Fiscal Year Final Research Report

• Project/Area Number: 26291002
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Molecular biology
• Research Institution: Tohoku University
• Principal Investigator: Inada Toshifumi 東北大学, 薬学研究科(研究院), 教授 (40242812)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 遺伝子発現の品質管理 / ナンセンス変異依存分解系 / Upf1 / Sse1 / Hsp70 / ユビキチン化 / プロテアソーム

Outline of Final Research Achievements

Accurate gene expression is the backbone of life phenomenon, and its breakdown and abnormality cause various diseases. In this research project, we aim to elucidate the degradation mechanism (NMPD) of gene products derived from abnormal mRNA, which is the earliest protein quality control mechanism. We analyzed short chain type proteolytic mechanism derived from abnormal mRNA with nonsense mutation, and obtained the following results. Sse1, an exchange factor for ADP/ATP of Hsp70, was required for promoting degradation of short chain type abnormal protein by Upf1. Mutant analysis of Sse1 revealed that interaction with Hsp70 is essential for NMPD. Moreover, it became clear that Sse1 does not promote the ubiquitination itself of short chain type abnormal protein itself. This study has led to an understanding of the molecular mechanism of NMPD, a degradation of truncated protein derived from abnormal mRNA with nonsense mutation.

Free Research Field

分子生物学