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Mechanism of TLP as a mediator in p53-p21 pathway

Research Project

Project/Area Number 24570193
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Molecular biology
Research InstitutionChiba University

Principal Investigator

Tamura Takaaki  千葉大学, 理学(系)研究科(研究院), 教授 (30112692)

Project Period (FY) 2012-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords転写制御因子 / TLP / p53 / TFIIA / TFⅡA / プロモーター / TATA-box / 転写制御 / p21
Outline of Final Research Achievements

We first examined the significance of p53 binding of TLP. We found that the p53 binding of TLP prevents p53 binding of MDM2, which destabilizes p53 via ubiquitin-proteasome system. This p53 binding of TLP results in concentration of p53 in the nucleus, which is antagonized by MDM2, and potentiates various p53 downstream genes. We suggest that TLP potentiates p53 both in transcriptional activation and protein stabilization. Second, we examined the significance of TFIIA binding of TLP. We found that the TLP binding results in inhibition of Taspase1-mediated processing of the precursor TFIIA. TLP potentiates transcription of TATA-less promoters but represses TATA promoters. Moreover, mature TFIIA is preferentially used for a preinitiation complex for TATA promoters. These mechanisms can explain why TLP inhibits TATA promoters. TLP may work as a molecular tuner for genomic gene expression. We also found that TFIIA stabilizes TLP, which is degraded by ubiquitin-proteasome system.

Report

(5 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (28 results)

All 2015 2014 2013 2012

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (17 results) (of which Int'l Joint Research: 2 results) Book (6 results)

  • [Journal Article] TBP-like protein (TLP) interferes with Taspase1-mediated processing of TFIIA and represses TATA box gene expression.2015

    • Author(s)
      Suzuki H, Isogai M, Maeda R, Ura K, Tamura T.
    • Journal Title

      Nucleic Acids Res

      Volume: 43 Issue: 13 Pages: 6285-6298

    • DOI

      10.1093/nar/gkv576

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Interaction between Transactivatton Domain of p53 and Middle Part of TBP-Like Protein (TLP) Is lnvolved in TLP-Stimulated and p53-Activated Transcription from the p21 Upstream Promoter.2014

    • Author(s)
      前田 亮、鈴木 秀文、田中 裕太、田村 隆明
    • Journal Title

      PLoS One

      Volume: 9 Issue: 3 Pages: e90190-e90190

    • DOI

      10.1371/journal.pone.0090190

    • Related Report
      2014 Research-status Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Activity of the upstream TATA-less promoter of the p21Waf1/Cip1 gene depends on transcription factor IIA (TFIIA) in addition to TFIIA-reactive TBP-like protein2014

    • Author(s)
      Hidefumi Suzuki, Ryo Maeda, Tomoyoshi Nakadai, and Taka-aki Tamura
    • Journal Title

      FEBS Journal

      Volume: 281 Issue: 14 Pages: 3126-3137

    • DOI

      10.1111/febs.12848

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] TATA-Binding Protein (TBP)-like protein is required for p53-dependent transcriptional activation of an upstream promoter of the p21^<Waf1/Cip1> gene2012

    • Author(s)
      Hidefumi Suzuki, Ryo Ito, Kaori Ikeda, Taka-aki Tamura
    • Journal Title

      J. Biol. Chem

      Volume: 287 Issue: 24 Pages: 19792-19803

    • DOI

      10.1074/jbc.m112.369629

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Interplay between two myogenesis-related proteins: TBP-interacting protein 120B and MyoD.2012

    • Author(s)
      Hidefumi Suzuki, Ai Suzuki, Yui Maekawa, Seiji Shiraishi and Taka-aki Tamura
    • Journal Title

      Gene

      Volume: 504 Issue: 2 Pages: 213-219

    • DOI

      10.1016/j.gene.2012.05.022

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] TFIIAによるTLPの安定化によるDNA傷害応答制御機構2015

    • Author(s)
      磯貝桃子、鈴木秀文、田村隆明
    • Organizer
      日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド(兵庫県、神戸市)
    • Year and Date
      2015-12-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] UV傷害時のp53ストレス応答におけるTBP-Like-Protein(TLP)の機能解析2015

    • Author(s)
      玉城寛之、前田亮、小島和華、鈴木秀文、田村隆明
    • Organizer
      日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド(兵庫県、神戸市)
    • Year and Date
      2015-12-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] TLPはマイオジェニンプロモーターを介して分化を抑制する2015

    • Author(s)
      中里有稀、鈴木秀文、田村隆明
    • Organizer
      日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド(兵庫県、神戸市)
    • Year and Date
      2015-12-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] Competitive p53 binding of TBP-like protein (TLP) against MDM2 induces stabilization of p53 and promotes p53-mediated cell growth regulation.2015

    • Author(s)
      Ryo Maeda, Hiroyuki Tamashiro, Kazunori Takano, Hidefumi Suzuki, Kiyoe Ura, Takeshi Endo, and Taka-aki Tamura
    • Organizer
      The 8th International MDM2 Workshop
    • Place of Presentation
      Tulane University Health Science Center School of Medicine (New Orleans, USA)
    • Year and Date
      2015-11-01
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] TBP-like protein (TLP) interferes with Taspase1-mediated processing of TFIIA and represses TATA box gene expression.2015

    • Author(s)
      H.Suzuki, M. Isogai, R. Maeda, K. Ura, and T. Tamura
    • Organizer
      Cold Spring Harbor Laboratory Meeting
    • Place of Presentation
      Cold Spring Harbor Laboratory (Cold Spring Harbor, USA)
    • Year and Date
      2015-08-25
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Function of TBP-Like Protein (TLP) in p53-governed cell growth regulation2014

    • Author(s)
      Ryo Maeda, Hiroyuki Tamashiro, Kazunori Takano, Hidefumi Suzuki, Takeshi Endo, and Taka-aki Tamura
    • Organizer
      The 2014 ASCB/IFCB Meeting
    • Place of Presentation
      Philadelphia, Pennsylvania, USA
    • Year and Date
      2014-12-06 – 2014-12-10
    • Related Report
      2014 Research-status Report
  • [Presentation] p53の細胞増殖制御機構におけるTBP-Like-Protein (TLP) の機能解析2014

    • Author(s)
      前田亮、玉城寛之、高野和儀、鈴木秀文、遠藤剛、田村隆明
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Research-status Report
  • [Presentation] TLPによるTFIIA結合性を介した遺伝子プロモーター調節機構2014

    • Author(s)
      鈴木秀文、磯貝桃子、中里有稀、前田亮、中太知義、田村隆明
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Research-status Report
  • [Presentation] TLPはTaspase1によるTFIIA前駆体の切断を阻害する2014

    • Author(s)
      中里有稀、鈴木秀文、田村隆明
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Research-status Report
  • [Presentation] TFIIA-mediated gene regulation by TLP. ASBMB Special Symposia Series, Transcriptional Regulation: Chromatin and RNA Polymerase II2014

    • Author(s)
      H. Suzuki, M. Isogai, A. Nakazato, R. Maeda, T. Nakadai, and T-A. Tamura
    • Organizer
      ASBMB Special Symposia Series, Transcriptional Regulation: Chromatin and RNA Polymerase II
    • Place of Presentation
      Snowbird, Utah, USA
    • Year and Date
      2014-10-02 – 2014-10-06
    • Related Report
      2014 Research-status Report
  • [Presentation] Interaction of TATA-binding protein-like protein (TLP) and transcription factor IIA is required for etoposide-induced activation of the upstream promoter of the p21Waf1/Cip1 Gene2014

    • Author(s)
      H. Suzuki, R. Maeda, T. Nakadai, and T-A. Tamura
    • Organizer
      Keystone Symposia
    • Place of Presentation
      Santa Fe, New Mexico, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] エトポシドによって誘導されるp21遺伝子上流プロモーターの活性化にはTLP-     TFIIAの相互作用が必要とされる2013

    • Author(s)
      鈴木秀文、前田亮、中太知義、田村隆明
    • Organizer
      日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Research-status Report
  • [Presentation] p21遺伝子転写におけるp53とTBP-like protein (TLP) の相互作用の解析2013

    • Author(s)
      前田亮、鈴木秀文、田村隆明
    • Organizer
      日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Research-status Report
  • [Presentation] Interaction between p53 and TATA-binding protein (TBP)-like protein2013

    • Author(s)
      R. Maeda, H. Suzuki, T-A. Tamura
    • Organizer
      Annual Meeting of the American Society for Cell Biology
    • Place of Presentation
      New Orleans, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] TATA-binding Protein (TBP)-like Protein Is Required for p53-dependent Transcriptional Activation of Upstream Promoter of p21Waf1/Cip1 Gene2012

    • Author(s)
      鈴木秀文、伊藤亮、池田香織、田村隆明
    • Organizer
      第12回日本分子生物学会春期シンポジウム
    • Place of Presentation
      石和
    • Related Report
      2012 Research-status Report
  • [Presentation] TLPによるp53依存的なp21遺伝子発現の活性化2012

    • Author(s)
      鈴木秀文、伊藤亮、池田香織、田村隆明
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      博多
    • Related Report
      2012 Research-status Report
  • [Presentation] TATA-Binding Protein (TBP)- Like Protein Is Required for p53-Dependent Transcriptional Activation of an Upstream Promoter of the p21Waf1/Cip1 Gene2012

    • Author(s)
      H. Suzuki, R. Ito, K. Ikeda, T-A. Tamura
    • Organizer
      Annual Meeting of the American Society for Cell Biology
    • Place of Presentation
      San Francisco, USA
    • Related Report
      2012 Research-status Report
  • [Book] 大学1年生のなっとく! 生物学2014

    • Author(s)
      田村隆明
    • Total Pages
      203
    • Publisher
      講談社
    • Related Report
      2014 Research-status Report
  • [Book] 改訂 バイオ試薬調製ポケットマニュアル2014

    • Author(s)
      田村隆明
    • Total Pages
      592
    • Publisher
      羊土社
    • Related Report
      2014 Research-status Report
  • [Book] コア講義・分子遺伝学2014

    • Author(s)
      田村隆明
    • Total Pages
      176
    • Publisher
      裳華房
    • Related Report
      2014 Research-status Report
  • [Book] しくみからわかる生命工学2013

    • Author(s)
      田村隆明
    • Total Pages
      216
    • Publisher
      裳華房
    • Related Report
      2013 Research-status Report
  • [Book] バイオ実験 安全ガイドブック2012

    • Author(s)
      田村隆明
    • Total Pages
      247
    • Publisher
      講談社
    • Related Report
      2012 Research-status Report
  • [Book] 基礎から学ぶ遺伝子工学2012

    • Author(s)
      田村隆明
    • Total Pages
      252
    • Publisher
      羊土社
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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