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Quantitative understanding of the mechanism of G1-S phase checkpoint regulated by ERK signal

Research Project

Project/Area Number 18H02444
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 44010:Cell biology-related
Research InstitutionCenter for Novel Science Initatives, National Institutes of Natural Sciences

Principal Investigator

AOKI Kazuhiro  大学共同利用機関法人自然科学研究機構(新分野創成センター、アストロバイオロジーセンター、生命創成探究, 生命創成探究センター, 教授 (80511427)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
KeywordsERK / Akt / 光遺伝学 / 細胞周期 / チェックポイント / RB / FRET / G1-S期チェックポイント / イメージング / G1/S / サイクリン / CDK
Outline of Final Research Achievements

The cell cycle, which determines whether cells divide or not, is an essential mechanism for living organisms. In this study, the activities of ERK and Akt, which are activated downstream of growth factors, were visualized at the single cell level by live-cell imaging, and the effects of their dynamics on the cell cycle were analyzed. We found that, (1) Akt shows a stochastic activation patterns similar to ERK, (2) there is a strong correlation between the activities of ERK and Akt, but there is a difference between them especially in the S phase, and (3) Akt activity is necessary for S/G2 progression, and (4) endocycling, which is a cell cycle progression without cytokinesis, occurs by inhibiting both ERK and Akt.

Academic Significance and Societal Importance of the Research Achievements

細胞の分裂、増殖は胚発生や再生といった生理的なプロセスと悪性腫瘍の増殖といった病理的な側面で起こる現象であり、細胞分裂を制御する細胞周期の理解は極めて重要である。本研究では、ERKとAktというどちらも多くの悪性腫瘍細胞で活性化が認められるシグナル伝達分子の細胞周期の役割を生細胞イメージングによってアプローチした研究であり、これまで知られていない結果を得ることができた。特に、Aktの細胞周期における役割のいくつかを今回の研究で明らかにすることができたことは今後の悪性腫瘍の治療戦略を考えるうえで重要になってくるものと考える。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (27 results)

All 2021 2020 2019 2018

All Journal Article (14 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 14 results,  Open Access: 10 results) Presentation (13 results) (of which Int'l Joint Research: 3 results,  Invited: 13 results)

  • [Journal Article] Visualization and Manipulation of Intracellular Signaling2021

    • Author(s)
      Goto Yuhei、Kondo Yohei、Aoki Kazuhiro
    • Journal Title

      Adv Exp Med Biol.

      Volume: 1 Pages: 225-234

    • DOI

      10.1007/978-981-15-8763-4_13

    • ISBN
      9789811587627, 9789811587634
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CDCP1 promotes compensatory renal growth by integrating Src and Met signaling2021

    • Author(s)
      Kajiwara Kentaro、Yamano Shotaro、Aoki Kazuhiro、Okuzaki Daisuke、Matsumoto Kunio、Okada Masato
    • Journal Title

      Life Science Alliance

      Volume: 4 Issue: 4 Pages: 202000832-202000832

    • DOI

      10.26508/lsa.202000832

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hierarchical modeling of mechano-chemical dynamics of epithelial sheets across cells and tissue2021

    • Author(s)
      Asakura Yoshifumi、Kondo Yohei、Aoki Kazuhiro、Naoki Honda
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 4069-4069

    • DOI

      10.1038/s41598-021-83396-6

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Signaling, Deconstructed: Using Optogenetics to Dissect and Direct Information Flow in Biological Systems2021

    • Author(s)
      Farahani Payam E.、Reed Ellen H.、Underhill Evan J.、Aoki Kazuhiro、Toettcher Jared E.
    • Journal Title

      Annual Review of Biomedical Engineering

      Volume: 23 Issue: 1 Pages: 61-87

    • DOI

      10.1146/annurev-bioeng-083120-111648

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 3DeeCellTracker, a deep learning-based pipeline for segmenting and tracking cells in 3D time lapse images2021

    • Author(s)
      Wen Chentao、Miura Takuya、Voleti Venkatakaushik、Yamaguchi Kazushi、Tsutsumi Motosuke、Yamamoto Kei、Otomo Kohei、Fujie Yukako、Teramoto Takayuki、Ishihara Takeshi、Aoki Kazuhiro、Nemoto Tomomi、Hillman Elizabeth MC、Kimura Koutarou D
    • Journal Title

      eLife

      Volume: 10

    • DOI

      10.7554/elife.59187

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A microtubule-LUZP1 association around tight junction promotes epithelial cell apical constriction2020

    • Author(s)
      Yano Tomoki、Tsukita Kazuto、Kanoh Hatsuho、Nakayama Shogo、Kashihara Hiroka、Mizuno Tomoaki、Tanaka Hiroo、Matsui Takeshi、Goto Yuhei、Komatsubara Akira、Aoki Kazuhiro、Takahashi Ryosuke、Tamura Atsushi、Tsukita Sachiko
    • Journal Title

      The EMBO Journal

      Volume: 40 Issue: 2

    • DOI

      10.15252/embj.2020104712

    • URL

      https://localhost/en/publications/5b8a970c-0f27-4635-b2eb-3af07674acb9

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Improvement of Phycocyanobilin Synthesis for Genetically Encoded Phytochrome-Based Optogenetics2020

    • Author(s)
      Uda Youichi、Miura Haruko、Goto Yuhei、Yamamoto Kei、Mii Yusuke、Kondo Yohei、Takada Shinji、Aoki Kazuhiro
    • Journal Title

      ACS Chemical Biology

      Volume: 15 Issue: 11 Pages: 2896-2906

    • DOI

      10.1021/acschembio.0c00477

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ERK-mediated mechanochemical waves direct collective cell polarization.2020

    • Author(s)
      Hino N, Rossetti L, Marin-Llaurad A, Aoki K, Trepat X, Matsuda M, Hirashima T.
    • Journal Title

      Developmental Cell

      Volume: 53 Issue: 6 Pages: 646-660

    • DOI

      10.1016/j.devcel.2020.05.011

    • NAID

      120006876575

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Engineering orthogonal, plasma membrane-specific SLIPT systems for multiplexed chemical control of signaling pathways in living single cells2020

    • Author(s)
      Akinobu Nakamura, Choji Oki, Kenya Kato, Satoko Fujinuma, Gembu Maryu, Keiko Kuwata, Tatsuyuki Yoshii, Michiyuki Matsuda, Kazuhiro Aoki, Shinya Tsukiji
    • Journal Title

      ACS Chemical Biology

      Volume: 15 Issue: 4 Pages: 1004-1015

    • DOI

      10.1021/acschembio.0c00024

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Improved secretion of glycoproteins using an N-glycan-restricted passport sequence tag recognized by cargo receptor2020

    • Author(s)
      Yagi Hirokazu、Yagi-Utsumi Maho、Honda Rena、Ohta Yusaku、Saito Taiki、Nishio Miho、Ninagawa Satoshi、Suzuki Kousuke、Anzai Takahiro、Kamiya Yukiko、Aoki Kazuhiro、Nakanishi Mahito、Satoh Tadashi、Kato Koichi
    • Journal Title

      Nature Communications

      Volume: 11 Issue: 1 Pages: 1-9

    • DOI

      10.1038/s41467-020-15192-1

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Single-cell quantification of the concentrations and dissociation constants of endogenous proteins2019

    • Author(s)
      Akira T Komatsubara, Yuhei Goto, Yohei Kondo, Michiyuki Matsuda, Kazuhiro Aoki
    • Journal Title

      Journal of Biological Chemistry

      Volume: 294 Issue: 15 Pages: 6062-6072

    • DOI

      10.1074/jbc.ra119.007685

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cell-to-Cell Heterogeneity in p38-Mediated Cross-Inhibition of JNK Causes Stochastic Cell Death2018

    • Author(s)
      Miura Haruko、Kondo Yohei、Matsuda Michiyuki、Aoki Kazuhiro
    • Journal Title

      Cell Reports

      Volume: 24 Issue: 10 Pages: 2658-2668

    • DOI

      10.1016/j.celrep.2018.08.020

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Composite regulation of ERK activity dynamics underlying tumour-specific traits in the intestine2018

    • Author(s)
      Muta Yu、Fujita Yoshihisa、Sumiyama Kenta、Sakurai Atsuro、Taketo M. Mark、Chiba Tsutomu、Seno Hiroshi、Aoki Kazuhiro、Matsuda Michiyuki、Imajo Masamichi
    • Journal Title

      Nature Communications

      Volume: 9 Issue: 1 Pages: 2174-2174

    • DOI

      10.1038/s41467-018-04527-8

    • NAID

      120006488609

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Live-cell Imaging with Genetically Encoded Protein Kinase Activity Reporters2018

    • Author(s)
      Maryu G, Miura H, Uda Y, Komatsubara AT, Matsuda M, Aoki K
    • Journal Title

      Cell Structure and Function

      Volume: 43 Issue: 1 Pages: 61-74

    • DOI

      10.1247/csf.18003

    • NAID

      130006725957

    • ISSN
      0386-7196, 1347-3700
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Visualization and manipulation of cell signaling and cell fates.2020

    • Author(s)
      Kazuhiro Aoki
    • Organizer
      Virtual Workshop: Cell State Transitions: Approaches, Experimental Systems and Models
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 蛍光イメージングを用いた細胞内シグナル伝達系の可視化・定量化・操作2020

    • Author(s)
      青木 一洋
    • Organizer
      NCU Life Science Seminar
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Live-cell quantification of the concentration and dissociation constant of endogenous proteins by a combination of CRISPR/Cas9 genome editing and FCS/FCCS.2019

    • Author(s)
      Kazuhiro Aoki
    • Organizer
      Interface between Immunology & Quantitative Biology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 細胞内シグナル伝達系の 可視化、定量化、光操作2019

    • Author(s)
      青木一洋
    • Organizer
      大阪大学蛋白質研究所セミナー がん研究の新機軸
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 生細胞イメージングによる細胞内シグナル伝達系の可視化、定量化、操作2019

    • Author(s)
      青木一洋
    • Organizer
      第9回光科学異分野横断萌芽研究会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 生細胞イメージングによるJNK活性の細胞間不均一性と確率的な細胞死の可視化2019

    • Author(s)
      青木一洋
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 遺伝子技術と生細胞イメージングによる内在性分子濃度と解離定数の定量化2019

    • Author(s)
      青木一洋
    • Organizer
      第60回日本組織細胞化学会総会・学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Visualization and manipulation of cell signaling2019

    • Author(s)
      Kazuhiro Aoki
    • Organizer
      The 2nd NIBB-Princeton Joint Symposium Imaging and Quantitative Biology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] イメージングによる細胞内シグナル伝達の定量化と操作2019

    • Author(s)
      青木一洋
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 細胞集団運動と非平衡輸送現象の接点2019

    • Author(s)
      青木 一洋
    • Organizer
      定量生物学の会第9回年会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 細胞内シグナル伝達系の可視化と光操作2018

    • Author(s)
      青木 一洋
    • Organizer
      第18回日本蛋白質科学会年会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 実験と数理モデルによる2018

    • Author(s)
      青木 一洋
    • Organizer
      第15回 生物数学の理論とその応用 -次世代の数理科学への展開-
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 細胞間のERK活性伝搬による細胞集団運動の制御と光操作2018

    • Author(s)
      青木 一洋
    • Organizer
      細胞を創る研究会11.0
    • Related Report
      2018 Annual Research Report
    • Invited

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Published: 2018-04-23   Modified: 2022-01-27  

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