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2010 Fiscal Year Final Research Report

The SCF ubiquitin ligase regulates calcineurin signaling through degradation of RCAN1, an inhibitor of calcineurin.

Research Project

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Project/Area Number 20570010
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Genetics/Genome dynamics
Research InstitutionThe Institute of Physical and Chemical Research

Principal Investigator

KISHI Tsutomu  The Institute of Physical and Chemical Research, 大学院・生命理工学研究科, グローバルCOE研究員 (80260024)

Project Period (FY) 2008 – 2011
Keywordsシグナル伝達 / 蛋白質分解 / カルシウム / ユビキチン
Research Abstract

The highly conserved RCAN family of proteins regulates the serine/threonine protein phosphatase calcineurin, which is required for the expression of genes involved in Ca^<2+->dependent processes such as the control of memory, apoptosis, T cell activation, cell cycle and cardiac muscle growth and differentiation. However, RCANs regulate calcineurin through two paradoxical actions: they act as feedback inhibitors of calcineurin, whereas their phosphorylation stimulates calcineurin. Here we showed that phosphorylation of RCAN triggers degradation through the SCF ubiquitin ligase complex in yeast and in human. Degradation of phosphorylated RCAN is required to mitigate inhibition of calcineurin by RCAN and results in activation of calcineurin in response to changes in Ca^<2+> concentration. Such phosphorylayion was counteracted by dephosphorylation of RCAN, which was promoted by Ca^<2+->stimulated calcineurin. These results provide insight into the mechanism involved in maintaining proper responses to Ca^<2+> signals.

  • Research Products

    (6 results)

All 2011 2009 2008 2007

All Journal Article (5 results) Book (1 results)

  • [Journal Article] SCF^<Dia2> regulates DNA replication forks during S-phase in budding yeast.2009

    • Author(s)
      Satomu Mimura, Makiko Komata, Tsutomu Kishi, Katsuhiko Shirahige, Takumi Kamura
    • Journal Title

      EMBO Journal 28

      Pages: 3693-3705

  • [Journal Article] A longevity protein, Lag2, interacts with SCF and regulates SCF function.2009

    • Author(s)
      Yuan Liu, Satoru Mimura, Tsutomu Kishi, Takumi Kamura
    • Journal Title

      EMBO Journal 28

      Pages: 3693-3705

  • [Journal Article] Oxidative-stress induced ubiquitination of RCAN1 mediated by SCF^<b-TrCP> ubiquitin ligase.2008

    • Author(s)
      Sachie Asada, Akemi Ikeda, Rina Nagao, Horoshi Hama, Tatsuhiko Sudo, Akiyoshi Fukamizu, Yoshihito Kasuya, Tsutomu Kishi
    • Journal Title

      International journal of molecular medicine 22

      Pages: 95-104

  • [Journal Article] A refined two-hybrid system reveals that SCF^<Cdc4>-dependent degradation of Swi5 contributes to the regulatory mechanism of S phase entry.2008

    • Author(s)
      Tsutomu Kishi, Akemi Ikeda, Noriko Koyama, Junji Fukada, Rina Nagao
    • Journal Title

      Proceedings of National Academy of Sciences (USA) 105

      Pages: 14497-14502

  • [Journal Article] The SCF^<Cdc4> ubiquitin ligase regulates calcineurin signaling through degradation of Rcn1, an inhibitor of calcineurin.2007

    • Author(s)
      Tsutomu Kishi, Akemi Ikeda, Rina Nagao, Noriko Koyama
    • Journal Title

      Proceedings of National Academy of Sciences (USA) 104

      Pages: 17418-17423

  • [Book] 目的別で選べる核酸実験の原理とプロとコール(酵母からの核酸抽出法)実験医学別冊(平尾一郎、胡桃坂仁志編集)2011

    • Total Pages
      145-151

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Published: 2012-01-26   Modified: 2016-04-21  

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