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Analysis of a novel regulatory mechanism "CLIP Model" of CDC-48, a AAA chaperone

Research Project

Project/Area Number 16K08594
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General medical chemistry
Research InstitutionKumamoto University

Principal Investigator

YAMANAKA KUNITOSHI  熊本大学, 発生医学研究所, 准教授 (90212290)

Project Period (FY) 2016-10-21 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords分子シャペロン / 線虫 / AAAシャペロン / CDC-48 / UBXN-6 / ユビキチン / 生体分子
Outline of Final Research Achievements

I found that both N and PUB domains, especially the PUB domain, of UBXN-6 are important for the interaction with CDC-48. In the mutant worms containing the PUB-domain-lacking UBXN-6, mutant UBXN-6 was not detected by Western blotting. Interestingly, it was however detected when the worms were treated with the proteasome inhibitor. These results suggested that the PUB-domain-lacking UBXN-6 can not properly interact with CDC-48 and free UBXN-6 molecules were degraded by the proteasome. This notion strongly supports the Clip model. I also found that the amount of UBXN-6 was increased upon starvation and that UBXN-6 is involved in the formation of late endosomes.

Academic Significance and Societal Importance of the Research Achievements

UBXN-6とCDC-48の相互作用様式を明らかにし、提唱した「クリップモデル」を支持する結果を得た。UBXN-6欠損株は短寿命を示すことも観察しており、これは細胞内タンパク質品質管理不全が一因となっている可能性が示唆された。CDC-48の変異に起因するヒト遺伝性疾患ALSやIBMPFDも知られており、タンパク質品質管理という観点からも今回得られた結果は、ヒト疾患の診断・予防・治療戦略の確立や創薬研究の基盤となることが期待される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (3 results)

All 2019 2018 2017

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

  • [Journal Article] Functional characterization of UBXN-6, a C-terminal cofactor of CDC-48, in C. elegans2019

    • Author(s)
      Mojumder Suman、Sawamura Rie、Murayama Yuki、Ogura Teru、Yamanaka Kunitoshi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 509 Issue: 2 Pages: 462-468

    • DOI

      10.1016/j.bbrc.2018.12.155

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of transgenic Caenorhabditis elegans expressing human transthyretin as a model for drug screening2018

    • Author(s)
      Tsuda Yukimoto、Yamanaka Kunitoshi、Toyoshima Risa、Ueda Mitsuharu、Masuda Teruaki、Misumi Yohei、Ogura Teru、Ando Yukio
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 17884-17884

    • DOI

      10.1038/s41598-018-36357-5

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Elucidation of UBXN-6 function in CDC-48-regulated ERAD in C. elegans2017

    • Author(s)
      Mojumder, S., Sawamura, R., Ogura, T., and Yamanaka, K.
    • Organizer
      第40回日本分子生物学会年会
    • Related Report
      2017 Research-status Report

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Published: 2016-10-24   Modified: 2020-03-30  

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