Formation mechanism of proteasome granules

• Project/Area Number: 24657097
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Functional biochemistry
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: SAEKI Yasushi 公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 副参事研究員 (80462779)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 細胞内タンパク質分解 / ユビキチン / プロテアソーム / 酵母 / 可逆性顆粒 / 蛍光相関分光法 / ミトコンドリア / ATP

Research Abstract

The proteasome is an ATP-dependent protease complex responsible for targeted protein degradation in eukaryotic cells. To identify factors that affect the proteasome dynamics, we screened a yeast mutant library and found that the proteasome formed a large cytoplasmic granule in almost all the mitochondrial mutants. We found that lowered cellular ATP levels induce the granule formation of the proteasome even in the wild-type cells. Importantly, the granule formation of the proteasome is conserved in yeast and humans. Furthermore, the purified proteasomes formed fibrous aggregated structures by ATP depletion. Taken together, these results suggest that the proteasome itself senses cellular ATP levels and autonomously forms reversible granule structure in responding to cellular environments.

Research Products

• [Journal Article] Structural Basis for Proteasome Formation Controlled by an Assembly Chaperone Nas2 (2014)
  • Author(s): Satoh T, Saeki Y, Hiromoto T, Wang YH, Uekusa Y, Yagi H, Yoshihara H, Yagi-Utsumi M, Mizushima T, Tanaka K, Kato K
  • Journal Title: Structure Volume: (掲載確定) Issue: 5 Pages: 731-743
  • DOI: 10.1016/j.str.2014.02.014
  • Peer Reviewed
• [Journal Article] Quantitative live-cell imaging reveals spatio-temporal dynamics and cytoplasmic assembly of the 26S proteasome (2014)
  • Author(s): Pack, CG., Yukii, H., Toh-e, A., Kudo, T., Tsuchiya, H., Kaiho, A., Sakata, E., Murata, S., Sako, Y., Baumeister, W., Tanaka, K., and Saeki, Y.
  • Journal Title: Nature Commun Volume: 5 Issue: 1 Pages: 3396-3396
  • DOI: 10.1038/ncomms4396
  • Peer Reviewed
• [Journal Article] The parallel reaction monitoring method contributes to highly sensitive polyubiquitin chain quantification. (2013)
  • Author(s): Tsuchiya, H., Tanaka, K., and Saeki, Y.
  • Journal Title: Biochem Biophys Res Commun. Volume: 436 Issue: 2 Pages: 223-229
  • DOI: 10.1016/j.bbrc.2013.05.080
  • Peer Reviewed
• [Journal Article] A multi-purpose fusion tag derived from an unstructured and hyper-acidic region of the amyloid precursor protein. (2013)
  • Author(s): Sangawa, T., Tabata, S., Suzuki, K., Saeki, Y., Tanaka, K., and Takagi, J.
  • Journal Title: Protein Science Volume: 22 Issue: 6 Pages: 840-850
  • DOI: 10.1002/pro.2254
  • Peer Reviewed
• [Journal Article] Structural basis for specific recognition of Rpt1p, an ATPase subunit of the 26S proteasome, by a proteasome-dedicated chaperone Hsm3p (2012)
  • Author(s): Takagi, T., et al
  • Journal Title: Journl of Biological Chemistry Volume: 287 Issue: 15 Pages: 12172-12182
  • DOI: 10.1074/jbc.m112.345876
  • Peer Reviewed
• [Journal Article] Proteasomal degradation resolves competition between cell polarization and cellular wound healing (2012)
  • Author(s): Kono, K., Saeki, Y., Yoshida, S., Tanaka, K., and Pellman, D.
  • Journal Title: Cell Volume: 150 Pages: 151-164
  • Peer Reviewed
• [Journal Article] Localization of the proteasomal ubiquitin receptors Rpn10 and Rpn13 by electron cryomicroscopy. (2012)
  • Author(s): Sakata E
  • Journal Title: Proc. Natl. Acad. Sci. USA. Volume: 109 Issue: 5 Pages: 1479-1484
  • DOI: 10.1073/pnas.1119394109
  • Peer Reviewed
• [Journal Article] The proteasome : molecular machinery and pathophysiological roles (2012)
  • Author(s): Tanaka, K., Mizushima, T., and Saeki, Y.
  • Journal Title: Biol Chem Volume: 393 Pages: 217-234
  • Peer Reviewed
• [Journal Article] Assembly and function of the proteasome (2012)
  • Author(s): Saeki, Y and Tanaka, K
  • Journal Title: Methods Mol Biol Volume: 832 Pages: 315-337
  • Peer Reviewed
• [Journal Article] Proteasomal degradation resolves competition between cell polarization and cellular wound healing. (2012)
  • Author(s): Kono K
  • Journal Title: Cell Volume: 150 Issue: 1 Pages: 151-164
  • DOI: 10.1016/j.cell.2012.05.030
  • Peer Reviewed
• [Presentation] 細胞内タンパク質分解装置プロテアソーム研究の最前線 (2014)
  • Author(s): 佐伯泰
  • Organizer: 金沢大学バイオAFM先端研究センターセミナー
  • Place of Presentation: 金沢
  • Year and Date: 2014-01-08
• [Presentation] Spatio-temporal dynamics and cytoplasmic assembly of the 26S proteasome (2014)
  • Author(s): Yasushi Saeki
  • Organizer: 231st IMEG seminars & Minisymposium “Recent advances and future directions in high-speed AFM imaging of ATP/GTP-driven molecular machinery”
  • Place of Presentation: Kumamoto, Japan
  • Invited
• [Presentation] ユビキチンコード解析法とプロテアソーム研究の最前線 (2013)
  • Author(s): 佐伯泰
  • Organizer: 東京工業大学フロンティア研究機構セミナー
  • Place of Presentation: 横浜
  • Year and Date: 2013-08-30
• [Presentation] プロテアソームダイナミクス (2013)
  • Author(s): 佐伯泰
  • Organizer: 理化学研究所シンポジウム「プロテアソームダイナミクスの理解を目指して」
  • Place of Presentation: 東京
  • Year and Date: 2013-01-17
• [Presentation] Quantitative Live-Cell Imaging Reveals Spatio- Temporal Dynamics and Cytoplasmic Assembly of the 26S Proteasome (2013)
  • Author(s): Yasushi Saeki, Chan-Gi Pack,1 Haruka Yukii, and Keiji Tanaka
  • Organizer: EMBO Conference on Ubiquitin and ubiquitin-like proteins"From structure to function"
  • Place of Presentation: Italy
• [Presentation] The formation mechanism of the proteasome granules (2013)
  • Author(s): Yasushi Saeki, Haruka Yukii, Naoko Arai, Ai Kaiho, and Keiji Tanaka
  • Organizer: The 35^<th> Natio Conference"The Ubiquitin-Proteasome System : From Basic Mechanisms to Pathophysiological Roles"
  • Place of Presentation: Sapporo
• [Presentation] プロテアソームは細胞内ATPレベルの低下を感知して顆粒を形成する (2013)
  • Author(s): 佐伯泰,雪井悠,田中啓二
  • Organizer: 第65回日本細胞生物学会大会シンポジウム「細胞の中の生々流転—「もの」の動態に基づく機能制御」
  • Place of Presentation: 名古屋
• [Presentation] プロテアソームは細胞内ATPレベルの低下を感知して顆粒を形成する (2013)
  • Author(s): 佐伯 泰、雪井 悠、田中啓二
  • Organizer: 第65回 日本細胞生物学会大会シンポジウム
  • Place of Presentation: 名古屋
  • Invited
• [Presentation] The formation mechanism of the proteasome granules (2013)
  • Author(s): Yasushi Saeki, Haruka Yukii, Naoko Arai, Ai Kaiho, and Keiji Tanaka
  • Organizer: The 35th Natio Conference “The Ubiquitin-Proteasome System: From Basic Mechanisms to Pathophysiological Roles”
  • Place of Presentation: Sapporo, Japan
  • Invited
• [Presentation] Quantitative Live-Cell Imaging Reveals Spatio-Temporal Dynamics and Cytoplasmic Assembly of the 26S Proteasome (2013)
  • Author(s): Yasushi Saeki, Chan-Gi Pack,1 Haruka Yukii, and Keiji Tanaka
  • Organizer: EMBO Conference on Ubiquitin and ubiquitin-like proteins “From structure to function”
  • Place of Presentation: Riva der Garda, Italy
• [Presentation] Structure and dynamics of the 26S proteasome (2012)
  • Author(s): Yasushi Saeki
  • Organizer: 熊本大学発生医学研究所リエゾンラボ研究会
  • Place of Presentation: 熊本
  • Year and Date: 2012-12-19
• [Presentation] 出芽酵母の休止期において形成されるプロテアソーム顆粒の解析 (2012)
  • Author(s): 雪井悠,新井直子,田中啓二,佐伯泰
  • Organizer: 第35回分子生物学会
  • Place of Presentation: 博多
  • Year and Date: 2012-12-14
• [Presentation] プロテアソーム可塑性 : 分子集合から顆粒形成まで (2012)
  • Author(s): 佐伯泰,雪井悠,土屋光,田中啓二
  • Organizer: 第85回日本生化学会大会シンポジウム
  • Place of Presentation: 博多
  • Year and Date: 2012-12-14
• [Presentation] 出芽酵母の休止期において形成されるプロテアソームストレージ顆粒の解析 (2012)
  • Author(s): 雪井悠,新井直子,田中啓二,佐伯泰
  • Organizer: 酵母遺伝学フォーラム第45回研究報告会
  • Place of Presentation: 宇治
  • Year and Date: 2012-09-05
• [Presentation] 細胞内タンパク質分解装置プロテアソームの分子集合と作動機構 (2012)
  • Author(s): 佐伯泰,坂田絵理,雪井悠,水島恒祐, W. Baumeister,田中啓二
  • Organizer: 酵母遺伝学フォーラム第45回研究報告会
  • Place of Presentation: 宇治
  • Year and Date: 2012-09-05
• [Presentation] 細胞内タンパク質分解装置プロテアソームの分子集合と作動機構 (2012)
  • Author(s): 佐伯泰,坂田絵理,白燦基,佐甲靖志, W. Baumeister,田中啓二
  • Organizer: 第12回日本蛋白質科学会年会
  • Place of Presentation: 名古屋
  • Year and Date: 2012-06-21
• [Presentation] 細胞内タンパク質分解装置プロテアソームの分子集合と作動機構
  • Author(s): 佐伯 泰
  • Organizer: 第12回日本蛋白質科学会年会
  • Place of Presentation: 名古屋
  • Invited
• [Presentation] 出芽酵母の休止期において形成されるプロテアソームストレージ顆粒の解析
  • Author(s): 雪井 悠、新井直子、田中啓二、佐伯 泰
  • Organizer: 酵母遺伝学フォーラム第45回研究報告会
  • Place of Presentation: 宇治
• [Presentation] プロテアソーム可塑性：分子集合から顆粒形成まで
  • Author(s): 佐伯 泰、雪井 悠、土屋 光、田中啓二
  • Organizer: 第85回日本生化学会大会シンポジウム
  • Place of Presentation: 博多
  • Invited
• [Presentation] 出芽酵母の休止期において形成されるプロテアソーム顆粒の解析
  • Author(s): 雪井 悠、新井直子、田中啓二、佐伯 泰
  • Organizer: 第35回分子生物学会
  • Place of Presentation: 博多
• [Presentation] プロテアソームダイナミクス
  • Author(s): 佐伯 泰
  • Organizer: 理化学研究所シンポジウム「プロテアソームダイナミクスの理解を目指して」
  • Place of Presentation: 和光
  • Invited
• [Book] プロテアソームの作動機構とダイナミクス「構造生命科学で何がわかるのか何ができるのか」実験医学・増刊号32巻(10号) (2014)
  • Author(s): 佐伯泰,水島恒裕
  • Publisher: 羊土社
• [Book] 実験医学・増刊号「構造生命科学－構造を使う研究を目指す新しいライフサイエンス」 (2014)
  • Author(s): 佐伯 泰、水島恒裕
  • Total Pages: 7
  • Publisher: 羊土社
• [Book] 細胞工学「Hot Press」 (2014)
  • Author(s): 佐伯 泰、白 燦基
  • Total Pages: 2
  • Publisher: 秀潤社
• [Book] 細胞膜修復機構におけるプロテアソームの役割.細胞工学31巻 (2012)
  • Author(s): 河野恵子,佐伯泰,吉田知史,田中啓二,David Pellman
  • Publisher: 秀潤社
• [Book] 巨大で複雑な蛋白分解装置の立体構造と活性調節機構.「特集/蛋白構造-機能連関解析と治療薬開発への応用」内分泌・糖尿病・代謝内科、第35巻12月号 (2012)
  • Author(s): 佐伯泰
  • Publisher: 科学評論社
• [Book] 細胞工学31巻 (2012)
  • Author(s): 河野恵子，佐伯 泰，吉田知史，田中啓二，David Pellman
  • Total Pages: 2
  • Publisher: 秀潤社
• [Book] 「特集／蛋白構造－機能連関解析と治療薬開発への応用」内分泌・糖尿病・代謝内科 (2012)
  • Author(s): 佐伯 泰
  • Total Pages: 10
  • Publisher: 科学評論社
• [Remarks]
  • URL: http://www.igakuken.or.jp/pro-meta/
• [Remarks] タンパク質分解酵素複合体「プロテアソーム」の動態を解明
  • URL: http://www.igakuken.or.jp/research/topics/2014/0306.html
• [Remarks] タンパク質分解酵素複合体「プロテアソーム」の動態を解明
  • URL: http://www.riken.jp/pr/press/2014/20140306_3/
• [Remarks] 公益財団法人東京都医学総合研究所蛋白質代謝研究室
  • URL: http://www.igakuken.or.jp/pro-meta/