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2013 Fiscal Year Final Research Report

Regulation of nuclear receptor activity by intracellular signals and ligands

Research Project

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Project/Area Number 23590324
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

SHIRAKI Takuma  近畿大学, 生物理工学部, 准教授 (10311747)

Co-Investigator(Renkei-kenkyūsha) IGARASHI Kazuhiko  東北大学, 大学院医学系研究科, 教授 (00250738)
Project Period (FY) 2011 – 2013
Keywords転写制御 / シグナル伝達 / セロトニン / エイコサノイド
Research Abstract

According to our previous findings of endogenous ligands for PPARg, we hypothesized that extracellular signaling molecules regulate PPARg activity through not only their intracellular metabolites acting as ligands, but also intracellular signals evoked by membrane associated receptors.
To analyze the temporal and spatial regulation of PPARg activity, we developed novel reporter system, by which six independent transcriptional activities were simultaneously detected. We found that expression of phosphorylation induced stabilization of PPARg proteins by itself and blocked nuclear export of PPARg protein only in the presence of SDP-1. We also analyzed the effects of PPARg mutation identified in German obese subjects on the phoshphorylation-dependent regulation, and found that P85Q mutation blocked the effects of SDP-1. Thus, we conclude that phosphorylation signal regulates PPARg activity in the distinct mechanism from that of ligands.

  • Research Products

    (13 results)

All 2014 2013 2012 2011

All Journal Article (5 results) (of which Peer Reviewed: 4 results) Presentation (5 results) Book (3 results)

  • [Journal Article] Hemopexin-dependent heme uptake via endocytosis regulates the Bach1 transcription repressor and heme oxygenase gene activation2014

    • Author(s)
      Hada, H., Shiraki, T., Watanabe-Matsui, M, Igarashi, K.
    • Journal Title

      BBA

      Volume: 1840 Pages: 2351-2360

    • DOI

      10.1016/j.bbagen.2014.02.029

    • Peer Reviewed
  • [Journal Article] Transactivation by Hesperetin Glucuronides is Distinct from That by a Thiazolidine-2,4-dione Agent2014

    • Author(s)
      Gamo, K., Shiraki, T., Matsuura, N., Miyachi, H.
    • Journal Title

      CHEM.PHARM.BULL.

      Volume: 62 Pages: 491-493

    • URL

      https://www.jstage.jst.go.jp/article/cpb/62/5/62_c14-00021/_article

    • Peer Reviewed
  • [Journal Article] Bach1 as a regulator of mitosis, beyond its transcriptional function2012

    • Author(s)
      Li, J., Shiraki, T. Igarashi, K.
    • Journal Title

      Communicative & Integrative Biology

      Volume: 5 Pages: 1-3

    • URL

      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3502211/

  • [Journal Article] Transcription-independent role of Bach1 in mitosis through a nuclear exporter Crm1-dependent mechanism2012

    • Author(s)
      Li, J., Shiraki, T., Igarashi, K.
    • Journal Title

      FEBS Lett.

      Volume: 586 Pages: 448-454

    • URL

      http://www.sciencedirect.com/science/article/pii/S0014579312000610

    • Peer Reviewed
  • [Journal Article] Detecting structural similarity of ligand interactions in the lipid metabolic system including enzymes, lipid binding proteins, and nuclear receptors.2011

    • Author(s)
      Shionyu-Matsuyama, C., Waku, T., Shiraki, T., Oyama, T., Shirai, T., Morikawa, K.
    • Journal Title

      PEDS

      Volume: 24 Pages: 397-403

    • URL

      http://peds.oxfordjournals.org/content/24/4/397.long

    • Peer Reviewed
  • [Presentation] Multiple metabolic pathways regulate PPARg in multiple ways2013

    • Author(s)
      Shiraki, T., Morikawa, K., Igarashi, K.
    • Organizer
      CSHL meeting
    • Place of Presentation
      Cold Spring Harbor Laboratory, NY, USA
    • Year and Date
      20130813-17
  • [Presentation] Structural basis for the activation of the nuclear receptor, PPARgamma, by fatty acid- and serotonin metabolites2012

    • Author(s)
      Waku, T., Shiraki, T., Morikawa, K.
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡国際会議場
    • Year and Date
      20121214-16
  • [Presentation] One receptor senses two ligands; the nuclear receptor PPARg monitors multiple cellular metabolism2012

    • Author(s)
      Shiraki, T., Morikawa, K., Igarashi, K.
    • Organizer
      Metabolism, Diet and Disease
    • Place of Presentation
      Georgetown University Hotel and Conference Center, Washington DC, USA
    • Year and Date
      20120529-31
  • [Presentation] 核内受容体PPARgの機能解析:分子生物学的アプローチと生化学的アプローチ2011

    • Author(s)
      白木琢磨
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      20110921-24
  • [Presentation] Sertonin metabolites act on the nuclear receptor PPARg as endogenous ligands independently of fatty-acid metabolites2011

    • Author(s)
      Shiraki, T., Morikawa, K., Igarashi, K.
    • Organizer
      LXXVI Cold Spring Harbor Symposium on Quantitative Biology
    • Place of Presentation
      Cold Spring Harbor Laboratory, NY, USA
    • Year and Date
      20110601-06
  • [Book] 生体内代謝物をモニターする転写システム:核内受容体PPARによる転写を介した代謝ネットワーク間のクロストーク(9月号)2013

    • Author(s)
      白木琢磨, 和久剛, 森川耿右
    • Total Pages
      749-761
    • Publisher
      生化学(日本生化学会)
  • [Book] 企画特集「タンパク質構造機能相関再考」(8月号)2013

    • Author(s)
      木下賢吾, 白木琢磨
    • Publisher
      生化学(日本生化学会)
  • [Book] 薬が作用するということ」化学と生物(3月号)2013

    • Author(s)
      白木琢磨
    • Total Pages
      193-195
    • Publisher
      国際文献社

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Published: 2015-07-16  

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