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2011 Fiscal Year Final Research Report

Screening for compounds targeted to novel rapamycin-independent autophagic mechanism

Research Project

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Project/Area Number 23659036
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Biological pharmacy
Research InstitutionKyoto University

Principal Investigator

KOZUTSUMI Yasunori  京都大学, 大学院・生命科学研究科, 教授 (70205425)

Co-Investigator(Kenkyū-buntansha) SANDO Yukari  京都大学, 大学院・生命科学研究科, 教務職員 (70359785)
Project Period (FY) 2011
Keywordsオートファジー / ラパマイシン / 酵母 / Ypk1 / スクリーニング / セリン・スレオニンキナーゼ
Research Abstract

In this grant, we established monitoring system of rapamycin-independent autophagic protein degradation utilizing GFP-tagged Ypk1 localization change under fluorescent microscope. In this assay, inhibitory activity of compounds could be monitored by the loss of vacuolar localization of Ypk1 when vacuolar peptidase deficient strain(pep4Δ) is used.This assay should be utilized along with primary screening system of normal protein degradation, namely Western blotting analysis after SDS-PAGE to monitor the degree of Ypk1 proteolysis. We also screened a set of yeast protein kinase mutant strains to understand the autophagic degradation of Ypk1. This screening was based on the hypothesis that intracellular signaling event is involved in the Ypk1 degradation. We have identified a pair of protein kinase that is responsible of Ypk1 phosphorylation both in vivo and in vitro. Data obtained here will be fundamentally required for future screening to target novel autophagic pathway.

  • Research Products

    (9 results)

All 2012 2011 2010

All Journal Article (5 results) (of which Peer Reviewed: 1 results) Presentation (3 results) Book (1 results)

  • [Journal Article] Tedder TFCD22 serves as a receptor for soluble IgM2012

    • Author(s)
      Adachi T, Harumiya S, Takematsu H, Kozutsumi Y, Wabl M, Fujimoto M
    • Journal Title

      Eur J Immunol

      Volume: 42(1) Pages: 241-247

    • Peer Reviewed
  • [Journal Article] Quantitative transcriptomic profiling of branching in a glycosphingolipid biosynthetic pathway2011

    • Author(s)
      Takematsu H, Yamamoto H, Naito-Matsui Y, Fujinawa R, Tanaka K, Okuno Y, Tanaka Y, Kyogashima M, Kannagi R, Kozutsumi Y
    • Journal Title

      Biol Chem

      Volume: 286(31) Pages: 27214-27224

  • [Journal Article] CD22-Antagonists with nanomolar potency : The synergistic effect of hydrophobic groups at C-2 and C-9 of sialic acid scaffold2011

    • Author(s)
      Abdu-Allah HHM, Watanabe K, Completo GC, Sadagopan M, Hayashizaki K, Takaku C, Tamanaka T, Takematsu H, Kozutsumi Y, Paulson JC, Tsubata T, Ando H, Ishida H, Kiso M
    • Journal Title

      Bioorg and Med Chem

      Volume: 19(6) Pages: 1966-71

  • [Journal Article] Sphingosylphosphorylcholine and lysosulfatide have inverse regulatory function in monocytic cell differentiation into macrophages2011

    • Author(s)
      Yamamoto H, Naito Y, Okano M, Kanazawa T, Takematsu H, Kozutsumi Y
    • Journal Title

      Arch Biochem Biophys

      Volume: 506(1) Pages: 83-91

  • [Journal Article] Identification of Ypk1 as a novel selective substrate for nitrogen starvation-triggered proteolysis requiring autophagy system and ESCRT machinery components2010

    • Author(s)
      Shimobayashi M, Takematsu H, Eiho K, Yamane Y, Kozutsumi Y
    • Journal Title

      J Biol Chem

      Volume: 285(47) Pages: 36984-94

  • [Presentation] Involvement of sphingolipids in phosphorylation and degradation of Ypk1 in the stress response of Yeast2011

    • Author(s)
      Y. Kozutsumi, M. Tomioka, M. Shimobayashi, Y. Yamane, H. Takematsu
    • Organizer
      The 31st NAITO conference on Glycan expression and regulation[II]
    • Place of Presentation
      Sapporo, Japan
    • Year and Date
      20110913-16
  • [Presentation] Regulatory Functions of Activation-Dependent Reduction of N-glycolylneuraminic Acid in Mouse T Cells2011 Annual Conference of the Society for Glycobiology2011

    • Author(s)
      Y. Naito-Matsui, H. Takematsu, K. Murata, Y. Kozutsumi
    • Place of Presentation
      シアトル(アメリカ)
    • Year and Date
      2011-11-10
  • [Presentation] スフィンゴ脂質とESCRT複合体が関与するYpk1の窒素源飢餓による分解2011

    • Author(s)
      下林貢、富岡真、山根ゆかり、竹松弘、小堤保則
    • Organizer
      第53回日本脂質生化学会
    • Place of Presentation
      東京
    • Year and Date
      2011-05-13
  • [Book] スフィンゴ脂質が関わる免疫抑制とシグナル伝達化学と生物2011

    • Author(s)
      竹松弘, 小堤保則
    • Total Pages
      49(05)
    • Publisher
      日本農芸化学会

URL: 

Published: 2013-07-31  

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