Functional regulation of novel tumor suppressor protein Sav1 by molecular chaperone

• Project/Area Number: 23590100
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Himeji Dokkyo University
• Principal Investigator: SHIBATA Katsushi 姫路獨協大学, 薬学部, 教授 (70296565)
• Co-Investigator(Kenkyū-buntansha): SHIRAKI Takashi 姫路獨協大学, 薬学部, 准教授 (10294208) ; SAKAI Nobuya 姫路獨協大学, 薬学部, 講師 (30525077)
• Co-Investigator(Renkei-kenkyūsha): KOSHIMIZU Taka-aki 自治医科大学, 医学部, 准教授 (20392491) ; IMANISHI Yorihisa 慶應義塾大学, 医学部, 講師 (80255538)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: Ｓａｖ１ / 分子シャペロン / アグレソーム / ミトコンドリア / 細胞周期 / 上皮間葉転換 / ユビキチン化

Research Abstract

Using high throughput proteomics screening, we identified the molecular chaperones (Hsp60 and Hsp70) as a novel protein associated with Sav1 (mammalian homologue of Salvador). Sav1 targets to the aggresome and its sequestration to the aggresome is enhanced by the proteasome inhibitor MG132. Furthermore, Sav1 co-localized with Hsp70 and CHIP (carboxy terminus of Hsp70-interacting protein) that has been shown to mediate substrate ubiquitination and degradation by the proteasome. In addition, anti-Sav1 immunostainings displayed partial colocalization with Hsp60. In this study, we demonstrate that Hsp60 is one of the proteins that binds to Sav1. The interaction between Hsp60 and Sav1 could influence the Hsp60-mediated signaling cascade. This study suggest that Sav1 has a previously unexpected critical role in the aggresome pathway.

Research Products

• [Presentation] 癌抑制因子RASSF1Aを介したがん抑制作用に関するPRMT5の機能的役割 (2014)
  • Author(s): 齊藤由美子
  • Organizer: 第8７回日本薬理学会年会
  • Place of Presentation: 仙台
• [Presentation] 新規がん抑制遺伝子Sav1の細胞増殖制御における役割-ヒトがん細胞を用いた検討- (2013)
  • Author(s): 酒井伸也
  • Organizer: 第86回日本薬理学会年会
  • Place of Presentation: 福岡
• [Presentation] Functional characterization of novel tumor suppressor protein Sav1 in cancer cell proliferation and epithelial-mesenchymal transition (2013)
  • Author(s): Sakai N
  • Organizer: 2013 Annual Meeting of the American Society for Biochemistry and Molecular Biology
  • Place of Presentation: Boston, Massachusetts, USA
• [Presentation] Functional characterization of novel tumor suppressor protein Sav1 in cancer cell proliferation and epithelial-mesenchymal transition. (2013)
  • Author(s): Ｎｏｂｕｙａ Ｓａｋａｉ
  • Organizer: 2013 Annual Meeting of the American Society for Biochemistry and Molecular Biology
  • Place of Presentation: Boston, Massachusetts, USA.
• [Presentation] Functional characterization of novel tumor suppressor protein Sav1 in human cancer cells (2013)
  • Author(s): 酒井伸也、柴田克志
  • Organizer: 第86回日本薬理学会年会
  • Place of Presentation: 福岡国際会議場
• [Presentation] Functional characterization of novel tumor suppressor protein Sav1 in cancer cell proliferatin and epithelial-mesenchymal transition (2013)
  • Author(s): 酒井伸也、柴田克志
  • Organizer: 2013年米国生化学・分子生物学会年会
  • Place of Presentation: Boston Convention and Exhibition Center （米国）
• [Presentation] アグレソーム形成におけるSav1の新たな機能 (2012)
  • Author(s): 酒井伸也
  • Organizer: 第59回日本生化学会近畿支部例会
  • Place of Presentation: 京都
  • Year and Date: 2012-05-19
• [Presentation] The novel role of Sav1 in aggresome formation (2012)
  • Author(s): Sakai N
  • Organizer: 2012 Annual Meeting of the American Society for Biochemistry and Molecular Biology
  • Place of Presentation: Diego, California, USA
• [Presentation] The novel role of Sav1 in aggresome formation (2012)
  • Author(s): 酒井 伸也
  • Organizer: 2012年米国生化学・分子生物学会
  • Place of Presentation: San Diego Convention Center(米国)