Regulatory mechanism of p62 gene expression

2014 Fiscal Year Final Research Report

• Project/Area Number: 23500434
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: MATSUMOTO Gen 独立行政法人理化学研究所, 脳科学総合研究センター, 客員研究員 (50415303)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Keywords: タンパク質分解 / 選択的オートファジー

Outline of Final Research Achievements

p62/Sqstm1 is a key molecule for the selective autophagy. To investigate how to induce p62 in cells, we performed a drug screening that activated or inactivated p62 promoter. For this aim, we cloned human 1.8 kbp of p62 promoter region and inserted GFP gene under the predicted translation starting points. Using this reporter constructs, we identified five p62-inducer candidates. Two of them were obviously able to reduce polyglutamine aggregation in cells, but the S403-phospholylated p62 were not accumulated. On the other hand, one of the five candidates enhanced the polyglutamine aggregate formation and the accumulation of S403-phospho-p62. This may be possible that the drug may interfere the constitutive autophagy. Our results suggests that p62 promoter can be modulated artificially and the appropriate induction of p62 may be beneficial to induce selective autophagy.

Free Research Field

分子細胞生物学