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Roles of BAG6 complex in nuclear protein quality contorol

Research Project

Project/Area Number 25840038
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Functional biochemistry
Research InstitutionTokyo Metropolitan University

Principal Investigator

YOKOTA Naoto  首都大学東京, 理工学研究科, 助教 (40610564)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
KeywordsBAG6 / 不良タンパク質 / 核内凝集体 / 不良タンパク質代謝 / 凝集体
Outline of Final Research Achievements

The protein quality control system plays a pivotal role in proteostasis in cells. Although it was reported that BAG6 is involved in recognition and degradation of misfolded newly synthesized proteins, and biogenesis of a group of transmembrane protein that does not have a signal sequence at its N-terminus, the precise roles of BAG6 in these processes and in the nucleus have not been elucidated yet.
I attempted to clarify roles of BAG6 and its cofactors such as TRC35, TRC40 and Ubl4a in the nucleus and revealed that TRC35 and dimerization of TRC40 are responsible for interaction between BAG6 and TRC40. In order to analyze the mechanism of misfolded protein degradation in the nucleus, we produced a model substrate conjugated a nuclear localization signal. We observed that degradation of the substrates abolished in the presence of proteasomal inhibitor but not in the presence of leptomycin.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (3 results)

All 2015 2014 2013

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (2 results)

  • [Journal Article] Structure of a BAG6 (Bcl-2-associated Athanogene 6)-Ubl4a (Ubiquitin-like Protein 4a) Complex Reveals a Novel Binding Interface That Functions in Tail-anchored Protein Biogenesis.2015

    • Author(s)
      Kuwabara N, Minami R, Yokota N, Matsumoto H, Senda T, Kawahara H, Kato R.
    • Journal Title

      J. Biol. Chem.

      Volume: 290 Issue: 15 Pages: 9387-9398

    • DOI

      10.1074/jbc.m114.631804

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] タンパク質品質管理システムにおけるTRC35/BAG6相互作用の意義2014

    • Author(s)
      田中花実,横田直人,川原裕之
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      兵庫県 神戸市
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Roles of mamalian GET components in BAG6-mediated protein control2013

    • Author(s)
      Naoto Yokota, Hiroyuki Kawahara
    • Organizer
      The 35th Naito Conference: The Ubiquitin-Proteasome system
    • Place of Presentation
      シャトレーゼガトーキングダム(北海道札幌市)
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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