Molecular mechanism of mammalian nuclear protein quality control

2016 Fiscal Year Final Research Report

• Project/Area Number: 25440097
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cell biology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Mizuno Takeshi 国立研究開発法人理化学研究所, 今本細胞核機能研究室, 専任研究員 (30281629)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: タンパク質品質管理 / 哺乳類細胞品質管理 / DNAポリメラーゼα / 温度感受性変異体細胞 / Novobiocin / HSP90 / タンパク質分解 / 哺乳類細胞核

Outline of Final Research Achievements

Due to a single point mutation in the DNA Polymerase alpha subunit p180, the temperature-sensitive cell cycle mouse cell line tsFT20 reveals a rapid de novo synthesis of p180tsFT20 in the cytoplasm and a proteasome-dependent degradation of nuclear localized protein. To further analyze the mechanism of nuclear degradation of aberrant Pol-alpha, we have searched chemicals those inhibit degradation of nuclear aberrant p180. We found that novobiocin, an HSP90 inhibitor, inhibits degradation of p180tsFT20 at non-permissive temperature in nucleus. To identify molecule participate in nuclear protein quality control, we carried out co-immunoprecitation analysis, and found that Chip (C terminus of Hsc-70 interacting protein) associated with HSP90 and colocalized in the nucleolus in the presence of novobiocin. Taken together, we have a working hypothesis that nuclear protein quality control mechanism involves nuclear HSP90.

Free Research Field

分子細胞生物学