Advanced investigation of molecular regulation of lipid metabolism by the transcription factor Nrf1

• Project/Area Number: 22590277
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Doshisha University
• Principal Investigator: KOBAYASHI Akira 同志社大学, 生命医科学部, 教授 (50292214)
• Co-Investigator(Kenkyū-buntansha): 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: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 脂質代謝異常 / 遺伝子発現制御 / タンパク質分解機構 / プロテアソーム / 転写制御 / ストレス応答 / タンパク質分解

Research Abstract

The experimental purpose of this project is to investigate regulatory mechanisms of the transcription factor Nrf1(NF-E2-related factor 1) for lipid metabolism. First, we found that the turnover of Nrf1 is regulated by the ubiquitin ligase Hrd1 and β-TrCP in the cytoplasm and nucleus, respectively. Second, we identified that proteasome subunit genes psmc4 and psmb6 were direct Nrf1 target genes.

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, S., Natsume, T., Yamamoto, M. and Kobayashi, A.
  • Journal Title: Mol. Cell. Biol. Volume: 31 Pages: 4500-4512
  • Peer Reviewed
• [Journal Article] Central nervous system-specific deletion of transcription factor Nrf1 causes progressive motor neuronal dysfunction (2011)
  • Author(s): Kobayashi, A., Tsukide, T., Miyasaka, T., Morita, T., Mizoroki, T., Saito, Y., Ihara, Y., Takashima, A., Noguchi, N., Fukamizu, A., Hirotsu, Y., Ohtsuji, M., Katsuoka, F. and Yamamoto, M.
  • Journal Title: Genes Cells Volume: 16 Pages: 692-703
  • Peer Reviewed
• [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
• [Journal Article] Central nervous system-specific deletion of transcription factor Nrf1 causes progressive motor neuronal dysfunction (2011)
  • Author(s): Kobayashi A, Tsukide T, Miyasaka T, Morita T, Mizoroki T, Saito Y, Ihara Y, Takashima A, Noguchi N, Fukamizu A, Hirotsu Y, Ohtsuji M, Katsuoka F, Yamamoto M
  • Journal Title: Genes Cells Volume: 16 Issue: 6 Pages: 692-703
  • DOI: 10.1111/j.1365-2443.2011.01522.x
  • Peer Reviewed
• [Journal Article] The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1 (2010)
  • Author(s): Komatsu, M., et al.
  • Journal Title: Nature Cell Biology Volume: 12 Pages: 213-223
  • Peer Reviewed
• [Journal Article] Crucial Role of Nrf3 in Smooth Muscle Cell Differentiation From Stem Cells. (2010)
  • Author(s): Pepe, A.E., et al.
  • Journal Title: Circulation Research Volume: 106 Pages: 870-879
  • Peer Reviewed
• [Presentation] Dual regulation of the transcriptional activity of Nrf1 by β-TrCP- and Hrd1-dependent degradation mechanisms (2011)
  • Author(s): 土谷佳樹
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(神奈川)
  • Year and Date: 2011-12-15
• [Presentation] CK2 regulates the transcriptional activity of Nrf1 to maintain cellular homeostasis (2011)
  • Author(s): 伊藤義起
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(神奈川)
  • 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: EMBO workshop on Intracellular Proteolysis & Cancer
  • Place of Presentation: Red Sea Mar Rojo Auditorium (Valencia, Spain)
  • Year and Date: 2011-10-27
• [Presentation] Dual regulation of the transcriptional activity of Nrf1 by β-TrCP-and Hrd1-dependent degradation mechanisms (2011)
  • Author(s): 土谷佳樹, 森田智子, 金美姫, 家村俊一郎, 夏目徹, 山本雅之, 小林聡
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] CK2 regulates the transcriptional activity of Nrf1 to maintain cellular homeostasis (2011)
  • Author(s): 伊藤義起, 土谷佳樹, 家村俊一郎, 夏目徹, 小林聡
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
• [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., and Kobayashi, A.
  • Organizer: EMBO Workshop on Intracellular Proteolysis and Cancer
  • Place of Presentation: Valencia, Spain
• [Presentation] Cytoplasmic and nuclear degradation mechanisms regulate biological function of the transcription factor Nrf1. (2010)
  • Author(s): 森田智子, 他
  • Organizer: 第33回日本分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド 神戸
  • Year and Date: 2010-12-09
• [Presentation] Central nervous system-specific deletion of transcription factor Nrf1 causes progressive motor neuronal dysfunction (2010)
  • Author(s): Tsukide T., et al.
  • Organizer: 5th International Symposium on GATA transcription factor
  • Place of Presentation: Gonryo-kaikan, Sendai
  • Year and Date: 2010-11-18
• [Presentation] リン酸化による転写因子Nrf1の機能制御機構の解析 (2010)
  • Author(s): 伊藤義起, 他
  • Organizer: 日本分子生物学会 第10回春季シンポジウム
  • Place of Presentation: ホテル松島大観荘、宮城県
  • Year and Date: 2010-06-07
• [Presentation] Cytoplasmic and nuclear degradation mechanisms regulate biological function of the transcription factor Nrf1 (2010)
  • Author(s): Morita, T., Tsuchiya, Y., Kim, M., Iemura, S., Tsukide, T., Natsume, T., Yamamoto, M., and Kobayashi, A.
  • Organizer: 第33回日本分子生物学会
  • Place of Presentation: 神戸
• [Presentation] CK2 regulates the transcription factor Nrf1 to maintain cellular homeostasis (2010)
  • Author(s): Ito, Y., Tsuchiya, Y., Iemura, S., Natsume, T., and Kobayashi, A.
  • Organizer: 6th International Conference on Protein Kinase CK2
  • Place of Presentation: Cologne, Germany
• [Presentation] Central nervous system-specific deletion of transcription factor Nrf1causes progressive motor neuronal dysfunction (2010)
  • Author(s): Tsukide, T., Kobayashi, A., Miyasaka, T. Morita, T., Mizoroki, T., Saito, Y., Ihara, Y. Takashima, A., Noguchi, N. Fukamizu, A., Hirotsu, Y., Ohtsuji, M., Katsuoka, F. and Yamamoto M
  • Organizer: 5th International Symposium on GATA transcription factor
  • Place of Presentation: Sendai, Japan
• [Presentation] リン酸化による転写因子Nrf1の機能制御機構解析 (2010)
  • Author(s): 伊藤義起, 土谷佳樹, 家村俊一郎, 夏目徹, 小林聡
  • Organizer: 分子生物学会第10回春季シンポジウム
  • Place of Presentation: 松島,宮城
• [Remarks]
  • URL: http://biomedical.doshisha.ac.jp/staff/index.html#gaku_ise