Mechanism of Nrf2-mediated self-renewal of hematopoietic stem cells

• Project/Area Number: 23659167
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: Tohoku University
• Principal Investigator: YAMAMOTO Masayuki 東北大学, 大学院・医学系研究科, 教授 (50166823)
• Co-Investigator(Kenkyū-buntansha): SHIMIZU Ritsu 東北大学, 大学院・医学系研究科, 教授 (40226262)
• Project Period (FY): 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
• Keywords: 転写因子 / 造血幹細胞 / 酸化ストレス

Research Abstract

It has been known that intracellular reaction oxygen specie (ROS)levels influence the maintenance of the stem cells. Nrf2 is a transcription factor that regulates the expression of antioxidant enzymes. In this study we analyzed the function of Nrf2 on hematopoietic system in mice. We found that Nrf2 negatively regulate cell-cycle progression of hematopoietic stem cells and contribute to the lineage commitment of multipotential progenitors.

Research Products

• [Journal Article] Mature erythrocyte membrane homeostasis is compromised by loss of the GATA1-FOG1 interaction (2012)
  • Author(s): Hasegawa A, Shimizu R, Mohandas N, Yamamoto M.
  • Journal Title: Blood Volume: 119 Pages: 2615-2623
  • Peer Reviewed
• [Journal Article] Mature erythrocyte membrane homeostasis is compromised by lass of the GATA1-FOG1 interaction (2012)
  • Author(s): Hasegawa A, Shimizu R, Mohandas N, Yamamoto M
  • Journal Title: Blood Volume: 11 Pages: 2615-2623
  • Peer Reviewed
• [Journal Article] Dysfunction of fibroblasts of extrarenal origin underlies renal fibrosis and renal anemia in mice (2011)
  • Author(s): Asada N, Takase M, Nakamura J, Oguchi A, Asada M, Suzuki N, Yamamura K, Nagoshi N, Shibata S, Rao TN, Fehling HJ, Fukatsu A, Minegishi N, Kita T, Kimura T, Okano H, Yamamoto M, Yanagita M.
  • Journal Title: J Clin Invest Volume: 121 Pages: 3980-3981
  • NAID: 120003338854
  • Peer Reviewed
• [Journal Article] Dual regulation of the transcriptional activity of Nrf1 by { beta}-TrCP-and Hrd1-dependent degradation mechanisms (2011)
  • Author(s): Tsuchiya Y, Morita T, Kim M, Iemura SI, Natsume T, Yamamoto M, and Kobayashi A.
  • Journal Title: Mol Cell Biol Volume: 31 Pages: 4500-4512
  • Peer Reviewed
• [Journal Article] Specific contribution of the erythropoietin gene 3' enhancer to hepatic erythropoiesis after late embryonic stages (2011)
  • Author(s): Suzuki N, Obara N, Pan X, Watanabe M, Jishage K, Minegishi N, and Yamamoto M.
  • Journal Title: Mol Cell Biol Volume: 31 Pages: 3896-3905
  • Peer Reviewed
• [Journal Article] Nrf2 regulates NGF mRNA induction by carnosic acid in T98G glioblastoma cells and normal human astrocytes (2011)
  • Author(s): Mimura J, Kosaka K, Maruyama A, Satoh T, Harada N, Yoshida H, Satoh K, Yamamoto M, and Itoh K.
  • Journal Title: J Biochem Volume: 150 Pages: 209-217
  • NAID: 10030587033
  • Peer Reviewed
• [Journal Article] Hirotsu Y, Katsuoka F, Itoh K, and Yamamoto M. Nrf2 degron-fused reporter system : a new tool for specific evaluation of Nrf2 inducers (2011)
  • Author(s): Hirotsu Y, Katsuoka F, Itoh K, and Yamamoto M.
  • Journal Title: Genes Cells Volume: 16 Pages: 406-415
  • Peer Reviewed
• [Journal Article] The Ufm1-activating enzyme Uba5 is indispensable for erythroid differentiation in mice (2011)
  • Author(s): Tatsumi, K., Yamamoto-Mukai, H., Shimizu, R., Waguri, S., Sou, Y-S., Sakamoto, A., Taya, C., Shitara, H., Hara, T., Chung, C.H., Tanana, K., Yamamoto, M., Komatsu, M.
  • Journal Title: Nat.Commun. Volume: 2 Issue: 1 Pages: 181-181
  • DOI: 10.1038/ncomms1182
  • Peer Reviewed
• [Journal Article] Nrf2 and selenoproteins are essential for maintaining oxidative homeostasis in erythrocytes and protecting against hemolytic anemia (2011)
  • Author(s): Kawatani Y, Suzuki T, Shimizu R, Kelly V, Yamamoto M.
  • Journal Title: Blood Volume: 177 Pages: 986-996
  • Peer Reviewed
• [Journal Article] Nrf2 and selenoproteins are essential for maintaining oxidative homeostasis in erythrocytes and protecting against hemolytic anemia (2011)
  • Author(s): Kawatani Y, Suzuki T, Shimizu R, Kelly V, Yamamoto M
  • Journal Title: Blood Volume: 117 Pages: 986-996
  • Peer Reviewed
• [Journal Article] Dysfunction of fibroblasts of extrarenal origin underlies renal fibrosis and renal anemia in mice (2011)
  • Author(s): Asada N, 他17名
  • Journal Title: J Clin Invest Volume: 121 Pages: 3981-3990
  • Peer Reviewed
• [Journal Article] Amino and carboxyl-terminal transactivation domains of GATA1 coordinate the hematopoietic program
  • Author(s): Kaneko H, Kobayashi E, Yamamoto M, Shimizu R.
  • Journal Title: J Biol Chem in press
  • Peer Reviewed
• [Presentation] ダウン症候群随伴巨核芽球性白血病の分子基盤 (2011)
  • Author(s): 清水律子
  • Organizer: 58回東北小児白血病研究
  • Place of Presentation: ホテルコムズ仙台
  • Year and Date: 2011-06-04
• [Presentation] ダウン症候群随伴巨核芽球性白血病の分子基盤 (2011)
  • Author(s): 清水律子
  • Organizer: 第58回東北小児白血病研究会
  • Place of Presentation: ホテルコムズ仙台
  • Year and Date: 2011-06-04
• [Presentation] Keap1 degradation by autophagy for the maintenance of redox homeostasis Discovery on Target (2011)
  • Author(s): Mitsuishi Y, Taguchi K, Motohashi H, Yamamoto M.
  • Organizer: Cancer Cell Metabolism as Drug Target
  • Place of Presentation: Park Plaza Hotel & Towers, Boston, MA, USA
• [Presentation] Select heterozygous Keap1 mutations have a dominant-negative effect on wild-type Keap1 in vivo (2011)
  • Author(s): Suzuki T, Maher J, Yamamoto M.
  • Organizer: 16th World Congress on Advances in Oncology and 14th International Symposium on Molecular Medicine
  • Place of Presentation: Rhodes Island, Greece
• [Presentation] Nrf2 activates the pentose phosphate pathway and glutamine consumption in proliferating cells (2011)
  • Author(s): Mitsuishi Y, Taguchi K, Yamamoto M, Motohashi H.
  • Organizer: 16th World Congress on Advances in Oncology and 14th International Symposium on Molecular Medicine
  • Place of Presentation: Rhodes, Island, Greece
• [Presentation] Transcription factor Nrf2 drives the pentosew phosphate pathway and glutamine consumption in proliferating cells (2011)
  • Author(s): Fujikawa N, Taguchi K, Motohashi H, Yamamoto M.
  • Organizer: 16th World Congress on Advances in Oncology and 14th International Symposium on Molecular Medicine
  • Place of Presentation: Rhodes, Island, Greece
• [Presentation] Select heterozygous Keap1 mutations have a dominant-negative effect on wild-type Keap1 in vivo (2011)
  • Author(s): Takafumi Suzuki, Jonathan Maher, Masayuki Yamamoto
  • Organizer: 16th World Congress on Advances in Oncology and 14th International Symposium on Molecular Medicine
  • Place of Presentation: Rhodes, Island, Greece
• [Presentation] Transcription factor Nrf2 drives the pentosew phosphate pathway and glutamine consumption proliferating cells (2011)
  • Author(s): Nanako Fujikawa, Keiko Taguchi, Hozumi Motohashi, Masayuki Yamamoto
  • Organizer: 16th World Congress on Advances in Oncology and 14th International Symposium on Molecular Medicine
  • Place of Presentation: Rhodes, Island, Greece
• [Presentation] Keap1 degradation by autophagy for the maintenance of redox homeostasis (2011)
  • Author(s): Yoichiro Mitsuishi, Keiko Taguchi, Hozumi Motohashi, Masayuki Yamamoto
  • Organizer: Discovery on Target, Cancer Cell Metabolism as Drug Target
  • Place of Presentation: Park Plaza Hotel & Towers, Boston, MA, USA