2010 Fiscal Year Final Research Report

Molecular mechanism underlying selective autophagy of aggregated protein

Research Project

Project/Area Number	21700398
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Single-year Grants
Research Field	Nerve anatomy/Neuropathology
Research Institution	The Institute of Physical and Chemical Research
Principal Investigator	MATSUMOTO Gen The Institute of Physical and Chemical Research, 構造神経病理研究チーム, 研究員 (50415303)
Project Period (FY)	2009 – 2010
Keywords	オートファジー / p62 / タンパク質分解 / シクエストソーム / ユビキチン
Research Abstract	The specific phosphorylation of p62 in its ubiquitin-associated (UBA) domain, regulates the autophagic clearance of polyubiquitinated protein aggregate. This phosphorylated form of p62 binds to polyubiquitin chains with higher affinity, resulting in the efficient recruitment of polyubiquitinated proteins in the "sequestosomes" which are units of autophagosome entry. The phosphorylation in p62 regulates autophagic clearance of ubiquitinated proteins that are poorly degraded by proteasomes.