Inhibition of tumor suppressor protein p53-dependent transcription by a tetramerization domain peptide via hetero-oligomerization

• Project/Area Number: 23651210
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Living organism molecular science
• Research Institution: Hokkaido University
• Principal Investigator: SAKAGUCHI Kazuyasu 北海道大学, 大学院・理学研究院, 教授 (00315053)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 蛋白質 / 核酸 / 酵素 / 生体分子 / 遺伝子 / へテロオリゴマー / 転写活性 / iPS細胞 / フラグメント縮合 / 蛋白質安定性

Research Abstract

In this study, we have developed a method for transient inhibition of p53-dependent transcription using a p53 tetramerization domain peptide that contains cell penetrating and nuclear localization signals. The peptide was efficiently introduced into cells and inhibited p21 expression via heterotetramerization with endogenous p53 protein. This method can be applied towards safe and efficient iPS cell generation.

Research Products

• [Journal Article] Silver nanocrystals formed by oligemeric biomineralization peptide via p53 tetramerization domain. (2013)
  • Author(s): T. Sakaguchi, J. I. Janairo, Y. Chuman, K. Hara, A. Fukuoka, and K. Sakaguchi
  • Journal Title: Peptide Sci. Volume: 2012 Pages: 57-58
  • Peer Reviewed
• [Journal Article] Silver nanocrystals formed by oligemeric biomineralization peptide via p53 tetramerization domain (2013)
  • Author(s): T. Sakaguchi
  • Journal Title: Peptide Science Volume: 2012 Pages: 57-58
  • Peer Reviewed
• [Journal Article] Inhibition of tumor suppressor protein p53-dependent transcription by a tetramerization domain peptide via hetero-oligomerization (2012)
  • Author(s): J. Wada, R. Kamada, Y. Chuman, T. Imagawa, and K. Sakaguchi
  • Journal Title: Bioorg Med Chem. Lett Volume: 22 Issue: 8 Pages: 2780-2783
  • DOI: 10.1016/j.bmcl.2012.02.085
  • Peer Reviewed
• [Journal Article] A small molecule inhibitor of p53-inducible protein phosphatase PPM1D (2012)
  • Author(s): 八木寛陽
  • Journal Title: Bioorganic & Medicinal Chemistry Letters Volume: VOL.22 Issue: 1 Pages: 729-732
  • DOI: 10.1016/j.bmcl.2011.10.084
  • Peer Reviewed
• [Journal Article] Repression of p53 transcriptional activity by inhibitory peptide via heterotetramerization (2012)
  • Author(s): J. Wada, R. Kamada, Y. Chuman, T.Imagawa, and K. Sakaguchi
  • Journal Title: Peptide Sci. Volume: 2011 Pages: 301-302
  • NAID: 10030204437
  • Peer Reviewed
• [Journal Article] Nanostructure formed bybiomineralization peptide oligomerized via p53 tetramerization (2012)
  • Author(s): T. Sakaguchi, R. Kamada, Y. Chuman, andK. Sakaguchi
  • Journal Title: Peptide Sci. Volume: 2011 Pages: 345-346
  • Peer Reviewed
• [Journal Article] Development of screening system for tumor suppressor p53 activators and inhibitors (2012)
  • Author(s): K. Uesugi, S. Oshima, A. Tanaka, T.Imagawa, and K. Sakaguchi
  • Journal Title: Peptide Sci. Volume: 2011 Pages: 403-404
  • NAID: 10030204653
  • Peer Reviewed
• [Journal Article] Repression of p53 transcriptional activity by inhibitory peptide via heterotetramerization (2012)
  • Author(s): J. Wada
  • Journal Title: Peptide Science Volume: 2011 Pages: 301-302
• [Journal Article] Nanostructure formed by biomineralization peptide oligomerized via p53 tetramerization (2012)
  • Author(s): T. Sakaguchi
  • Journal Title: Peptide Science Volume: 2011 Pages: 345-346
  • NAID: 10030204547
• [Journal Article] Development of screening system for tumor suppressor p53 activators and inhibitors (2012)
  • Author(s): K. Uesugi
  • Journal Title: Peptide Science Volume: 2011 Pages: 403-404
• [Journal Article] Formation process and solvent-dependent structure of a polyproline self-assembled monolayer on a gold surface (2011)
  • Author(s): Y.Han
  • Journal Title: Langmuir Volume: 27 Issue: 19 Pages: 11951-11957
  • DOI: 10.1021/la2020995
  • Peer Reviewed
• [Presentation] 癌抑制タンパク質p53の四量体形成ドメインにおけるアルギニン残基修飾の構造安定性に対する効果 (2013)
  • Author(s): J.Wada
  • Organizer: 第13回日本蛋白質科学会年会
  • Place of Presentation: とりぎん文化会館(鳥取県)
• [Presentation] 癌抑制タンパク質p53の四量体形成ドメインにおけるアルギニン残基修飾の構造安定性に対する効果 (2013)
  • Author(s): J. Wada
  • Organizer: 第13回日本蛋白質科学会年会
  • Place of Presentation: とりぎん文化会館（鳥取県）
• [Presentation] p53標的遺伝子プロモーターに対する内因性p53依存的転写活性の蛍光解析系 (2012)
  • Author(s): T.Higashi
  • Organizer: 第49回日本生化学会北海道支部例会
  • Place of Presentation: 北海道大学(札幌市)
  • Year and Date: 2012-07-20
• [Presentation] Formation of Palladium Nanosponges by an Oligomerized Biomineralization Peptide through the p53Tetramerization Domain (2012)
  • Author(s): J.I.B. Janairo
  • Organizer: 第49回ペプチド討論会
  • Place of Presentation: かごしま県民交流センター(鹿児島県)
• [Presentation] Silver Nanocrystals Formed by Oligemeric Biomineralization Peptide via p53 Tetramerization Domain (2012)
  • Author(s): T. Sakaguchi
  • Organizer: 第49回ペプチド討論会
  • Place of Presentation: かごしま県民交流センター(鹿児島県)
• [Presentation] Biomineralization and nanoparticle arrangement by Oligomeric Peptides (2012)
  • Author(s): K. Sakaguchi
  • Organizer: Cambodian Malaysian Chemical Conference 2012
  • Place of Presentation: Angkor Century Resort and Spa(カンボジア)
• [Presentation] 癌抑制タンパク質p53に対する一過性ペプチド阻害剤の開発 (2012)
  • Author(s): J.Wada,etal.
  • Organizer: 日本化学会秋季事業-第2回CSJ化学フェスタ2012
  • Place of Presentation: 東京工業大学(東京都目黒区)
• [Presentation] Control of Biomineralization and Nanoparticle Arrangement via Peptide Self-assembly (2012)
  • Author(s): K. Sakaguchi
  • Organizer: 14th Akabori Conference
  • Place of Presentation: ニセコ町民センター(北海道)
• [Presentation] p53四量体形成ドメインを介した多量体バイオミネラリゼーションペプチドによる銀粒子形成 (2012)
  • Author(s): T.Sakaguchi
  • Organizer: 第92日本化学会春季年会
  • Place of Presentation: 慶應義塾大学(横浜市)
• [Presentation] 癌抑制タンパク質p53転写活性に対するペプチド阻害剤 (2012)
  • Author(s): J.Wada
  • Organizer: 第92日本化学会春季年会
  • Place of Presentation: 慶應義塾大学(横浜市)
• [Presentation] Control of Biomineralization and Nanoparticle Arrangement via Peptide Self-assembly (2012)
  • Author(s): K. Sakaguchi
  • Organizer: 14th Akabori Conference
  • Place of Presentation: ニセコ町民センター（北海道）
  • Invited
• [Presentation] Biomineralization and nanoparticle arrangement by Oligomeric Peptides (2012)
  • Author(s): K. Sakaguchi
  • Organizer: Cambodian Malaysian Chemical Conference 2012
  • Place of Presentation: Angkor Century Resort and Spa (カンボジア)
  • Invited
• [Presentation] p53標的遺伝子プロモーターに対する内因性p53依存的転写活性の蛍光解析系 (2012)
  • Author(s): T. Higashi
  • Organizer: 第49回日本生化学会北海道支部例会
  • Place of Presentation: 北海道大学（札幌市）
• [Presentation] 癌抑制タンパク質p53に対する一過性ペプチド阻害剤の開発 (2012)
  • Author(s): J. Wada
  • Organizer: 日本化学会秋季事業－第2回CSJ化学フェスタ2012
  • Place of Presentation: 東京工業大学（東京都目黒区）
• [Presentation] Formation of Palladium Nanosponges by an Oligomerized Biomineralization Peptide through the p53 Tetramerization Domain (2012)
  • Author(s): J.I.B. Janairo
  • Organizer: 第49回ペプチド討論会
  • Place of Presentation: かごしま県民交流センター （鹿児島県）
• [Presentation] Silver Nanocrystals Formed by Oligemeric Biomineralization Peptide via p53 Tetramerization Domain (2012)
  • Author(s): T. Sakaguchi
  • Organizer: 第49回ペプチド討論会
  • Place of Presentation: かごしま県民交流センター （鹿児島県）
• [Presentation] p53四量体形成ドメインを介した多量体バイオミネラリゼーションペプチドによる銀粒子形成 (2012)
  • Author(s): T. Sakaguchi
  • Organizer: 第92日本化学会春季年会
  • Place of Presentation: 慶應義塾大学（横浜市）
• [Presentation] 癌抑制タンパク質p53転写活性に対するペプチド阻害剤 (2012)
  • Author(s): J. Wada
  • Organizer: 第92日本化学会春季年会
  • Place of Presentation: 慶應義塾大学（横浜市）
• [Presentation] 生細胞蛍光イメージングを利用した癌抑制タンパク質p53の機能解析 (2011)
  • Author(s): T.Imagawa
  • Organizer: 第48回日本生化学会北海道支部例会
  • Place of Presentation: 札幌医科大学(札幌市)
  • Year and Date: 2011-08-05
• [Presentation] ヘテロオリゴマー形成を介したp53転写活性阻害ペプチドの開発 (2011)
  • Author(s): J.Wada
  • Organizer: 日本化学会北海道支部2011年夏季研究発表会
  • Place of Presentation: 室蘭工業大学(室蘭市)
  • Year and Date: 2011-07-23
• [Presentation] Development of screening system for tumor suppressor p53 activators and inhibitors (2011)
  • Author(s): K. Uesugi
  • Organizer: 第48回ペプチド討論会
  • Place of Presentation: 札幌コンベンションセンター(北海道)
• [Presentation] Nanostructure formed by biomineralization peptide oligomerized via p53 tetramerization (2011)
  • Author(s): T. Sakaguchi
  • Organizer: 第48回ペプチド 討論会
  • Place of Presentation: 札幌コンベンショ ンセンター(北海道)
• [Presentation] Repression of p53 transcriptional activity by inhibitory peptide via heterotetramerization (2011)
  • Author(s): J. Wada
  • Organizer: 第48回ペプチ ド討論会
  • Place of Presentation: 札幌コンベンションセンター(北海道)
• [Presentation] Arrangement of Nanoparticle and Biomineralization through Peptide Self-assembly (2011)
  • Author(s): K. Sakaguchi
  • Organizer: 14th Asian Chemical Congress 2011
  • Place of Presentation: The Queen Sirikit National Convention Center(タイ)
• [Presentation] Methylation of p53Tetramerization Domain Arginine Residues Destabilizes the Tetrameric Structure (2011)
  • Author(s): K. Sakaguchi
  • Organizer: 22nd American Peptide Symposuim
  • Place of Presentation: Sheraton Hotel and Marina(アメリカ)
• [Presentation] Arrangement of Nanoparticle and Biomineralization through Peptide Self-assembly (2011)
  • Author(s): K. Sakaguchi
  • Organizer: 14th Asian Chemical Congress 2011(招待講演)
  • Place of Presentation: he Queen Sirikit National Convention Center （タイ）
• [Presentation] Methylation of p53 Tetramerization Domain Arginine Residues Destabilizes the Tetrameric Structure (2011)
  • Author(s): K. Sakaguchi
  • Organizer: 22nd American Peptide Symposuim
  • Place of Presentation: Sheraton Hotel and Marina（アメリカ）
• [Presentation] ヘテロオリゴマー形成を介したp53転写活性阻害ペプチドの開発 (2011)
  • Author(s): J. Wada
  • Organizer: 日本化学会北海道支部 2011年 夏季研究発表会
  • Place of Presentation: 室蘭工業大学（室蘭市）
• [Presentation] 生細胞蛍光イメージングを利用した癌抑制タンパク質p53の機能解析 (2011)
  • Author(s): T. Imagawa
  • Organizer: 第48回日本生化学会北海道支部例会(招待講演)
  • Place of Presentation: 札幌医科大学（札幌市）
• [Presentation] Development of screening system for tumor suppressor p53 activators and inhibitors (2011)
  • Author(s): K. Uesugi
  • Organizer: 第48回ペプチド討論会
  • Place of Presentation: 札幌コンベンションセンター （北海道）
• [Presentation] Nanostructure formed by biomineralization peptide oligomerized via p53 tetramerization (2011)
  • Author(s): T. Sakaguhi
  • Organizer: 第48回ペプチド討論会
  • Place of Presentation: 札幌コンベンションセンター （北海道）
• [Presentation] Repression of p53 transcriptional activity by inhibitory peptide via heterotetramerization (2011)
  • Author(s): J. Wada
  • Organizer: 第48回ペプチド討論会
  • Place of Presentation: 札幌コンベンションセンター （北海道）
• [Remarks]
  • URL: http://wwwchem.sci.hokudai.ac.jp/~biochem/index.html