Phosphorylation-mediated regulation of Nrf1 in the pathogenesis of steatohepatitis

• Project/Area Number: 22790329
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Pathological medical chemistry
• Research Institution: Doshisha University
• Principal Investigator: TSUCHIYA Yoshiki 同志社大学, 生命医科学部, 助教 (30456777)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 代謝異常学 / 細胞・組織 / シグナル伝達 / 脂質

Research Abstract

I identified β-TrCP and CK2 as Nrf1-binding proteins. I found that β-TrCP regulates Nrf1 degradation in the nucleus and its transcriptional activity(Tsuchiya et al.(2011) Mol. Cell. Biol. 31 : 4500-4512). I also found that CK2 phosphorylates Nrf1 and suppresses its transcriptional activity, thereby impairs Nrf1-dependent induction of proteasome gene expression. These results suggest that phosphorylation of Nrf1 is a novel therapeutic target for ameliorating accumulation of protein aggregates observed in steatohepatitis and neurodegenerative diseases.

Research Products

• [Journal Article] Dual Regulation of the Transcriptional Activity of Nrf1 by β-TrCP-and Hrd1-Dependent Degradation Mechanisms (2011)
  • Author(s): Tsuchiya Y, Morita T, Kim M, Iemura SI, Natsume T, Yamamoto M, Kobayashi A
  • Journal Title: Mol Cell Biol Volume: 31 Issue: 22 Pages: 4500-4512
  • DOI: 10.1128/mcb.05663-11
  • Peer Reviewed
• [Presentation] Dual regulation of the transcriptional activity of Nrf1 by β-TrCP-and Hrd1-dependent degradation mechanisms (2011)
  • Author(s): Tsuchiya Y, Morita T, Kim M, Iemura S, Natsume T, Yamamoto M, Kobayashi A
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-15
• [Presentation] Dual regulation of the transcriptional activity of Nrf1 by β-TrCP- and Hrd1-dependent degradation mechanisms (2011)
  • Author(s): Yoshiki Tsuchiya
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(横浜)
  • Year and Date: 2011-12-15
• [Presentation] Dual Regulation of the Transcription Factor Nrf1(Nfe2l1) by β-TrCP-And Hrd1-Dependent Degradation Mechanisms (2011)
  • Author(s): Tsuchiya Y, Morita T, Kim M, Iemura S, Natsume T, Yamamoto M, Kobayashi A
  • Organizer: EMBO Workshop on Intracellular Proteolysis & Cancer
  • Place of Presentation: スペイン,バレンシア
  • Year and Date: 2011-10-26
• [Presentation] The role of CK2 in the regulation of the mammalian circadian rhythms (2010)
  • Author(s): Yoshiki Tsuchiya
  • Organizer: 6^<th> International Conference on Protein Kinase CK2
  • Place of Presentation: Wahn Castle, Cologne, Germany
  • Year and Date: 2010-09-10