Regulation of the tumor suppressor p53 by Bach1

• Project/Area Number: 19390068
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Tohoku University
• Principal Investigator: IGARASHI Kazuhiko Tohoku University, 大学院・医学系研究科, 教授 (00250738)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000); Fiscal Year 2008: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000); Fiscal Year 2007: ¥12,350,000 (Direct Cost: ¥9,500,000、Indirect Cost: ¥2,850,000)
• Keywords: 遺伝子 / ストレス / 蛋白質 / 発現制御 / 免疫学

Research Abstract

がん抑制因子p53の作用機構として, 細胞老化の誘導がある。細胞老化は安定な不可逆的な細胞増殖停止状態であり, 発がん防御にも重要とされている。しかし, p53による細胞老化誘導の制御機構については不明な点が多い。本研究では, 転写因子Bach1がp53の働きを阻害することに着目し, その分子機構の解明に取り組んだ。その結果, Bach1-p53相互作用の制御機構, Bach1-p53により制御される老化実行遺伝子セットを明らかにし,さらに, Bach1が発癌促進因子として作用する可能性を見いだした。

Research Products

• [Journal Article] Crystal structure of the Bach1 BTB domain and its regulation of homodimerization (2009)
  • Author(s): Ito N., Watanabe-Matsui M., Igarashi K., and Murayama K
  • Journal Title: Genes Cells 14 Pages: 1365-2443
• [Journal Article] Crystal structure of the Bachl BTB domain and its regulation of homodimerization (2009)
  • Author(s): Ito, N., et.al.
  • Journal Title: Genes Cells 14 Pages: 1365-2443
  • Peer Reviewed
• [Journal Article] Genetic ablation of transcription repressor Bachl reduces neural tissue damage and improves locomotor function after spinal cord iniury in mice (2009)
  • Author(s): Kanno, H., et.al.
  • Journal Title: J. Neurotrauma. (in press)
  • Peer Reviewed
• [Journal Article] Bach1 inhibits oxidative stress-induced cellular senescence by impeding p53 function on chromatin (2008)
  • Author(s): Dohi, Y., Ikura, T., Hoshikawa, Y., Katoh, Y., Ota, K., Nakanome, A., Muto, A., Omura, S., Ohta, T., Ito, A., Yoshida, M., Noda, T., and Igarashi, K
  • Journal Title: Nature Struct. Mol. Biol 15 Pages: 1246-1254
• [Journal Article] Bachl inhibits oxidative stress-induced cellular senescence by impeding p53 function on chromatin (2008)
  • Author(s): Dohi, Y., et.al.
  • Journal Title: Nature Struct. Mol. Biol. 15 Pages: 1246-1254
  • Peer Reviewed
• [Journal Article] Bachl modulates heme oxygenase-1 expression in the neonatal mouse lung (2008)
  • Author(s): Kassaovska-Bratinova, S., et.al.
  • Journal Title: Pediatr. Res. (in press)
  • Peer Reviewed
• [Journal Article] Oxidative stress reaction in the meniscus of bachl deficient mice : Potential prevention of meniscal degeneration (2008)
  • Author(s): Ochiai, S., et.al.
  • Journal Title: J. Orthop. Res. 26 Pages: 894-898
  • Peer Reviewed
• [Journal Article] Myocardial Protection Against Pressure Overload in Mice Lacking Bachl, a Transcriptional Repressor of Heme Oxygenase-1 (2008)
  • Author(s): Mito, S., et.al.
  • Journal Title: Hypertension 51 Pages: 1570-1577
  • Peer Reviewed
• [Journal Article] Ablation of the bachl gene leads to the suppression of atherosclerosis in bachl and apolipopro E double knockout mice (2008)
  • Author(s): Watari, Y., et.al.
  • Journal Title: Hypertens. Res. 31 Pages: 783-792
  • Peer Reviewed
• [Journal Article] Heme induces ubiquitination and degradation of the transcription factor Bach1 (2007)
  • Author(s): Zenke-Kawasaki, Y., Dohi, Y., Katoh, Y., Ikura, T., Ikura, M., Asahara, T., Tokunaga, F., Iwai, K., and Igarashi, K
  • Journal Title: Mol. Cell. Biol 27 Pages: 6962-6971
• [Journal Article] Bach1 repression of Ferritin and thioredoxin reductase1 is heme-sensitive in cells and in vitro, and coordinates expression with heme oxygenase1, beta-globin and NADP(H) quinone(oxido)reductase1 (2007)
  • Author(s): Hintze, K.J., Katoh, Y., Igarashi, K., and Theil, E.C
  • Journal Title: J. Biol. Chem 282 Pages: 34365-34371
• [Journal Article] Heme induces ubiquitination and degradation of the transcription factor Bachl. (2007)
  • Author(s): Zenke-Kawasaki, Y., et. al.
  • Journal Title: Mol. Cell. Biol. 27 Pages: 6962-6971
  • Peer Reviewed
• [Journal Article] Bachl repression of Ferritin and thioredoxin reductasel is heme-sensitive in cells and in vitro, and coordinates expression with heme oxygenasel, beta-globin and NADP(H)quinone(oxido)reductasel. (2007)
  • Author(s): Hintze, K. J., et. al.
  • Journal Title: J. Biol. Chem. 282 Pages: 34365-34371
  • Peer Reviewed
• [Journal Article] DNA damage-dependent acetylation and ubiquitination of H2AX enhances chromatin dynamics. (2007)
  • Author(s): Ikura T., et. al.
  • Journal Title: Mol. Cell. Biol. 27 Pages: 7028-7040
  • Peer Reviewed
• [Presentation] Bach1-p53 complex mediates histone deacetylation at p53 target genes and sets threshold for cellular senescence (2008)
  • Author(s): Dohi, Y., Ikura, T., Hoshikawa, Y., Noda, T., and Igarashi, K
  • Organizer: Asian Forum of Chromosome and Chromatin Biology and symposium on Nuclear Architecture and Chromatin Dynamics,
  • Place of Presentation: Hderabad, India
  • Year and Date: 2008-11-27