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Pim-1 kinase activates Cdc25A phosphatase, the transcriptional target of c-Myc

Research Project

Project/Area Number 11671354
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionThe University of Tokyo

Principal Investigator

MOCHIZUKI Toshihiro  The University Hospital, Neurosurgery, Staff, 医学部・付属病院, 助手 (30302706)

Co-Investigator(Kenkyū-buntansha) ASAI Akio  The University Hospital, Neurosurgery, Assistant Professor, 医学部・付属病院, 講師 (50231858)
植木 敬介  東京大学, 医学部・付属病院, 助手 (20302705)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordspim-1 / c-myc / cdc25A / apoptosis / アポートシス / 遺伝子治療
Research Abstract

The pim-1 oncogene encodes a serine/threonine kinase (Pim-1) involved in the transduction of cytokine-triggered mitogenic signals. Pim-1 is unique in that it closely cooperates with c-Myc not only in oncogenesis but also in apoptosis induction. However, the molecular basis of Pim-1 function remains poorly understood, largely because the downstream effector molecule (s) for Pim-1 kinase has not been identified. Here we provide several lines of evidence that Cdc25A cell cycle phosphatase, a direct transcriptional target for c-Myc, is a substrate for Pim-1 kinase and functions as an effector for Pim-1. We found that Pim-1 physically interacts with Cdc25A both in vitro and in vivo and phosphorylates Cdc25A.We also observed that Pim-1-mediated phosphorylation of Cdc25A increases its phosphatase activity. In addition, wild-type Pim-1, but not kinase-inactive Pim-1, enhanced Cdc25A-mediated cellular transformation and apoptosis. Our results indicate that Cdc25A might be a key molecule that links Pim-1 and c-Myc and also ties Pim-1-mediated mitogenic signals to cell cycle machinery.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Mochizuki T,Kitanaka C,Noguchi K,Muramatsu T,Asai A,Kuchino Y: "Physical and functional interactions between Pim-1 kinase and Cdc25A phosphatase. Implications for the Pim-1-mediated activation of the c-Myc signaling pathway."J Biol Chem. 274(26). 18659-18666 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Chi S,Kitanaka C,Noguchi K,Mochizuki,T,Nagashima Y,Shirouzu M,Fujita H,Yoshida M,Chen W,Asai A,Himeno M,Yokoyama S,Kuchino Y.: "Oncogenic Ras triggers cell suicide through the activation of a caspase-independent cell death program in human cancer cells."Oncogene. 18(13). 2281-2290 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Noguchi K,Kitanaka C,Yamana H,Kokubu A,Mochizuki T,Kuchino Y.: "Regulation of c-Myc through phosphorylation at Ser-62 and Ser-71 by c-Jun N-terminal kinase"J Biol Chem. 274(46). 32580-32587 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Noguchi K,Yamana H,Kitanaka C,Mochizuki T.Kokubu A,Kuchino Y: "Differential role of the JNK and p38 MAPK pathway in c-Myc- and s-Myc-mediated apoptosis"Biochem Biophys Res Commun. 267(1). 221-227 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mochizuki T, Kitanaka C, Noguchi K, Muramatsu T, Asai A, Kuchino Y: "Physical and functional interactions between Pim-1 kinase and Cdc25A phosphatase. Implications for the Pim-1-mediated activation of the c-Myc signaling pathway."J Biol Chem.. 274(26). 18659-66 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Chi S, Kitanaka C, Noguchi K, Mochizuki T, Nagashima Y, Shirouzu M, Fujita H, Yoshida M, Chen W, Asai A, Himeno M, Yokoyama S, Kuchino Y: "Oncogenic Ras triggers cell suicide through the activation of a caspase-independent cell death program in human cancer cells"Oncogene.. 18(13). 2281-90 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Noguchi K, Kitanaka C, Yamana H, Kokubu A, Mochizuki T, Kuchino Y: "Regulation of c-Myc through phosphorylation at Ser-62 and Ser-71 by c-Jun N-terminal kinase"J Biol Chem.. 274(46). 32580-7 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Noguchi K, Yamana H, Kitanaka C, Mochizuki T, Kokubu A, Kuchino Y: "Differential role of the JNK and p38 MAPK pathway in c-Myc- and s-Myc- mediated apoptosis"Biochem Biophys Res Commun.. 267(1). 221-7 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Noguchi K,Yamana H,Kitanaka C,Mochizuki T,Kokubu A,Kuchino Y: "Differential role of the JNK and p38 MAPK pathway in c-Myc-and s-Myc-mediated apoptosis "Biochem Biophys Res Commun. 267(1). 221-227 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Mochizuki T, Kitanaka C, Noguchi K, Muramatu T, Asai A, and Kuchino Y: "Physical and Functional Interactions between Pim-1 Kinase and Cdc25A Phosphatase"The Journal of Biological Chemistry. Vol.274,No26. 18659-18666 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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