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Understanding the anchoring disruptor or modulator of subunits of the exocyst provides a new therapeutic strategy for various diseases.

Research Project

Project/Area Number 18K06815
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 48010:Anatomy-related
Research InstitutionYamagata University

Principal Investigator

Tanaka Toshiaki  山形大学, 医学部, 客員研究員 (70536987)

Project Period (FY) 2018-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords開口分泌小胞 / 脱リン酸化 / Sec6 / ジアシルグリセロールキナーゼ / PP2A / 脂質二重膜 / プロテインフォスファターゼ / 開口分泌 / 開口分泌複合体 / HSP27 / Secファミリー / リン脂質代謝酵素 / エキソソーム
Outline of Final Research Achievements

Sec6 is one of the subunits of the exocyst, an evolutionarily conserved eight-protein complex comprising Sec3 (EXOC1), Sec5 (EXOC2), Sec6 (EXOC3), Sec8 (EXOC4), Sec10 (EXOC5), Sec15 (EXOC6), Exo70 (EXOC7) and Exo84 (EXOC8) subunits. Recently, several researches have showed that Sec6 is associated with various cellular mechanisms such as neurite growth, cell adhesion, cell polarity, cell migration, cell cycle, NFκB signaling, and apoptosis. These functions may be dependent or independent on its basic role of Sec6 in exocytosis.
However, the relationship between Sec6 and PP2A in the Raf-MEK-ERK-p90RSK cascade is still largely unclear. We demonstrate that Sec6 regulates PP2A phosphatase activity through the modulation of the binding of PP2A-A and PP2Ac subunit, thereby modulating the phosphorylation of p90RSK at Thr359 and Ser380 and glycogen synthase kinase 3β at Ser9 and the expression of zinc finger E-box binding homeobox 1 (ZEB1), Vimentin, and zonula occludens 3 (ZO-3).

Academic Significance and Societal Importance of the Research Achievements

今回の研究において、開口分泌小胞の構成要素の1つであるSec6が、細胞内でのある特定タンパク質の脱リン酸化に関与し、様々な疾患に関わる可能性を提示した。開口分泌小胞は、唾液、血液、尿に含まれており、現在では比較的容易に回収・解析が可能である。開口分泌小胞の構成要素の研究が進み、様々な病態に関与することがさらに解明されれば、非侵襲的な方法で病気の早期発見や病態把握に寄与できる。また、開口分泌小胞の構成要素をターゲットとした新たな薬剤の開発につながると考えられる。

Report

(7 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (7 results)

All 2021 2020 2019 2018

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results) Funded Workshop (1 results)

  • [Journal Article] Regulation of p53 and NF-κB transactivation activities by DGKζ in catalytic activity-dependent and -independent manners2021

    • Author(s)
      Tanaka Toshiaki、Nakano Tomoyuki、Hozumi Yasukazu、Martelli Alberto M.、Goto Kaoru
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

      Volume: 1868 Issue: 4 Pages: 118953-118953

    • DOI

      10.1016/j.bbamcr.2021.118953

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] DGKζ depletion attenuates HIF-1α induction and SIRT1 expression, but enhances TAK1-mediated AMPKα phosphorylation under hypoxia2020

    • Author(s)
      Akimoto Ryo、Tanaka Toshiaki、Nakano Tomoyuki、Hozumi Yasukazu、Kawamae Kaneyuki、Goto Kaoru
    • Journal Title

      Cellular Signalling

      Volume: 71 Pages: 109618-109618

    • DOI

      10.1016/j.cellsig.2020.109618

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Knockdown of DEAD-box RNA helicase DDX5 selectively attenuates serine 311 phosphorylation of NF-κB p65 subunit and expression level of anti-apoptotic factor Bcl-2.2020

    • Author(s)
      Tanaka K, Tanaka T*, Nakano T, Hozumi Y, Yanagida M, Araki Y, Iwazaki K, Takagi M, Goto K
    • Journal Title

      Cellular Signalling

      Volume: 65 Pages: 1-8

    • DOI

      10.1016/j.cellsig.2019.109428

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] DzMab-1: Anti-Human Diacylglycerol Kinaseζ Monoclonal Antibody for Immunocytochemistry.2019

    • Author(s)
      Nakano T, Ogasawara S, Tanaka T, Hozumi Y, Sano M, Sayama Y, Yamada S, Shirai Y, Kaneko MK, Kato Y, Goto K
    • Journal Title

      Monoclonal antibodies in immunodiagnosis and immunotherapy

      Volume: 38 Issue: 4 Pages: 179-182

    • DOI

      10.1089/mab.2019.0024

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Nucleosome assembly proteins NAP1L1 and NAP1L4 modulate p53 acetylation to regulate cell fate.2019

    • Author(s)
      Tanaka T, Hozumi Y, Martelli AM, Iino M, Goto K
    • Journal Title

      BBA Molecular Cell Research

      Volume: 1866 Issue: 12 Pages: 1-13

    • DOI

      10.1016/j.bbamcr.2019.118560

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Sec6 enhances cell migration and suppresses apoptosis by elevating the phosphorylation of p38 MAPK, MK2, and HSP272018

    • Author(s)
      Tanaka Toshiaki、Iino Mitsuyoshi、Goto Kaoru
    • Journal Title

      Cellular Signalling

      Volume: 49 Pages: 1-16

    • DOI

      10.1016/j.cellsig.2018.04.009

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Funded Workshop] ASCB Annual Meeting2018

    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2025-01-30  

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