• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

A novel regulatory mechanism of the function of tumor suppressor p27 by a nucleolar protein NPM1.

Research Project

Project/Area Number 21K05510
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 38060:Applied molecular and cellular biology-related
Research InstitutionTokyo University of Agriculture

Principal Investigator

CHIBAZAKURA TAKU  東京農業大学, 生命科学部, 教授 (30227334)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2023: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords細胞増殖制御 / p27 / NPM1 / ARF / p53 / タンパク質分解 / 細胞遊走・浸潤能 / がん転移 / 足場非依存的増殖 / タンパク質間相互作用
Outline of Research at the Start

細胞増殖のブレーキ因子であり、がん抑制因子でもあるp27の機能制御は、動物細胞の増殖制御に重要であり、その破綻はがん化の要因の一つである。本研究は、新規に分離したp27の抑圧因子NPM1によるp27機能制御の分子機構について、細胞レベル及び動物個体レベルで解明するとともに、多種のがんにおいてNPM1によるp27機能抑圧が普遍的であるかを明らかにするものである。さらに、p27-NPM1間の相互作用を干渉することによってp27機能の回復を試み、p27の機能制御を標的とした新規抗がん戦略の有効性を検討する。

Outline of Final Research Achievements

The dysfunction of the cyclin-dependent kinase inhibitor/tumor suppressor p27 is one of the contributing factors to carcinogenesis. In this study, we elucidated that NPM1, a p27-interacting factor highly expressed in cancers, suppresses p27 function by trapping it in the nucleolus. Additionally, we revealed that another tumor suppressor, ARF, restores p27 function by inhibiting NPM1. We also discovered that p27 protein degradation is accelerated in the absence of the major tumor suppressor p53 and suggest that p53 negatively regulates two pathways of p27 degradation. Furthermore, we demonstrated that induction of p27 expression in cancer cells not only inhibits cell proliferation but also suppresses factors contributing to cancer malignancy, such as cell migration, invasion, and metastatic potential.

Academic Significance and Societal Importance of the Research Achievements

本研究で示されたNPM1によるp27機能制御機構は、p27を十分量発現していながら増殖が正常に制御されないがん細胞におけるp27の機能抑圧機構とともに、その抑圧を打ち消すがん抑制因子ARFの重要性を示唆するものとして新規性・学術的意義ともに高い。また、がん細胞でNPM1-p27相互作用を阻害することでp27機能を回復させるような新規抗がん戦略への応用も期待され、社会的意義も高い。さらに、最も主要ながん抑制因子p53によるp27安定化機構、およびp27が転移に関わるがん悪性化要因を抑制する機能を新規に見出したことは、p27を軸とするがん抑制ネットワークの理解に大きく貢献するものである。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (2 results)

All 2023 2022

All Journal Article (2 results) (of which Peer Reviewed: 2 results)

  • [Journal Article] Development of a novel co-culture system using human pancreatic cancer cells and human iPSC-derived stellate cells to mimic the characteristics of pancreatic ductal adenocarcinoma in?vitro2023

    • Author(s)
      Kometani Tatsuya、Kamo Koki、Kido Taketomo、Hiraoka Nobuyoshi、Chibazakura Taku、Unno Kenji、Sekine Keisuke
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 658 Pages: 1-9

    • DOI

      10.1016/j.bbrc.2023.03.061

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Differential regulation of p27Kip1 depending on culture conditions and its correlation with status of p14ARF and p532022

    • Author(s)
      Kometani Tatsuya、Kawasaki Yutaro、Chibazakura Taku
    • Journal Title

      Genes to Cells

      Volume: 27 Issue: 3 Pages: 229-237

    • DOI

      10.1111/gtc.12919

    • Related Report
      2021 Research-status Report
    • Peer Reviewed

URL: 

Published: 2021-04-28   Modified: 2025-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi