Transcription factor regulation of malignant cell transformation and its repression

• Project/Area Number: 15027201
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: University of Tsukuba
• Principal Investigator: YAMAMOTO Masayuki University of Tsukuba Institute of Basic Medical sciences, Professor, 基礎医学系, 教授 (50166823)
• Co-Investigator(Kenkyū-buntansha): 大根田 絹子 筑波大学, 大学院・人間総合科学研究科, 講師 (50323291) ; 清水 律子 筑波大学, 大学院・人間総合科学研究科, 講師 (40226262)
• Project Period (FY): 2003 – 2004
• Project Status: Completed (Fiscal Year 2004)
• Budget Amount: ¥59,000,000 (Direct Cost: ¥59,000,000); Fiscal Year 2004: ¥29,500,000 (Direct Cost: ¥29,500,000); Fiscal Year 2003: ¥29,500,000 (Direct Cost: ¥29,500,000)
• Keywords: GATA-1 knockdown mouse / Apoptosis / Erythroid differentiation / Myelodysplastic syndrome / Leukemia / Down syndrome / GATA-1 / GATA-2 / 造血 / トランスジェニックマウス / 転写因子 / 赤血球 / 細胞分化

Research Abstract

In this study we have studied transcription factor regulation of malignant cell transformation and its repression exploiting hematopoietic transcription factors and leukemia as a model system. GATA-1 is essential for the development of erythroid and megakaryocytic lineages and mutations leading to the production of N-terminus truncated form GATA-1 are frequently found in the Down syndrome-related acute megakaryoblastic leukemia (AMKL-DS) patients. We found that GATA-1 gene knockdown female (GATA-1.05/X) mice frequently develop a hematopoietic disorder that resembles myelodysplastic syndrome characterized by the accumulation of progenitors. We have demonstrated that GATA-1.05/X mice suffer from two distinct types of acute leukemias. Since GATA-1 is an X chromosomal gene, two types of hematopoietic cells reside within heterozygous GATA-1 knockdown mice, bearing either an active wild-type GATA-1 allele or an active mutant GATA-1.05 allele. In the latter hematopoietic progenitors, low-level GATA-1 expression is sufficient to support survival, but not differentiation, leading to the accumulation of progenitors that are easily targeted by oncogenic stimuli. Since such leukemia cases have not been observed in GATA-1-null/X mutant mice and since transgenic expression of wild-type GATA-1 rescue GATA-1.05/X mice from the leukemia, we conclude that the residual GATA-1 activity in the knockdown mice contributes to the development of the malignancy. In addition, wild-type GATA-1 promoted AMKL-DS leukemic cells to mature erythroid cells, but truncated form GATA-1 could not, suggesting that defect of GATA-1 is one of the leukemogenic factors.

Research Products

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  • Description: 「研究成果報告書概要(和文)」より
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  • Description: 「研究成果報告書概要(和文)」より
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  • Journal Title: Arch. Biochem. Biophys. 433 Pages: 342-350
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Purification, crystallization and preliminary X-ray diffraction analysis of the Kelch-like motif region of mouse Keap1. (2005)
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  • Journal Title: Acta Crystallographica 61 Pages: 153-155
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] An activator protein-l-Notch-4 angiogenic vascular remodeling pathway. (2005)
  • Author(s): Wu, J., et al.
  • Journal Title: Mol. Cell. Biol. 25 Pages: 1458-1474
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Transgenic overexpression of GATA-1 mutant lacking N-finger domain causes hemolytic syndrome in mouse erythroid cells. (2005)
  • Author(s): Nakano, M., Ohneda, K., Mukai, H.Y., Shimizu, R., Ohneda, O., Ohmura, S., Suzuki, M., Tsukamoto, S., Yanagawa, T., Yoshida, H., Takakuwa, Y., Yamamoto, M.
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• [Journal Article] Nrf2 transcriptionally activates the mafG gene through an antioxidant response element. (2005)
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  • Journal Title: J.Biol.Chem. 280 Pages: 4483-4490
• [Journal Article] Evolutionary conserved N-terminal domain of Nrf2 is essential for the Keap1-mediated degradation of the protein by proteasome. (2005)
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  • Journal Title: Arch.Biochem.Biophys. 433 Pages: 342-350
• [Journal Article] Purification, crystallization and preliminary X-ray diffraction analysis of the Kelch-like motif region of mouse Keap1. (2005)
  • Author(s): Padmanabhan, B., Scharlock, M., Tong, K.I., Nakamura, Y., Kang, M-I., Kobayashi, A., Matsumoto, T., Tanaka, A., Yamamoto, M., Yokoyama, S.
  • Journal Title: Acta Crystallographica 61 Pages: 153-155
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  • Journal Title: Biochem.J. (印刷中)
• [Journal Article] UVA irradiation induces Nrf2 activation in dermal fibroblasts : Protective role in UVA-induced apoptosis. (2005)
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• [Journal Article] Molecular mechanisms activating Nrf2-Keap1 pathway in regulation of antioxidant genes. (2005)
  • Author(s): Kobayashi, M., Yamamoto, M.
  • Journal Title: Antioxidants Redox Signaling 7 Pages: 384-395
• [Journal Article] Gene expression regulation and domain function of hematopoietic GATA factors. (2005)
  • Author(s): Shimizu, R., Yamamoto, M.
  • Journal Title: Seminars in Cell & Developmental Biology 16 Pages: 129-136
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  • Journal Title: Mol.Cell.Biol. 25 Pages: 1215-1217
• [Journal Article] Transcription factor Nrf2 regulates inflammation by mediating the effect of 15-deoxy-Δ^<12,14>-prostaglandin J_2. (2004)
  • Author(s): Itoh, K., et al.
  • Journal Title: Mol. Cell. Biol. 24 Pages: 36-45
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Characterization of the pufferfish Otx2 cis-regulators reveals evolutionarily conserved genetic mechanisms for the vertebrate head specification. (2004)
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• [Journal Article] Evaluation of MafG interaction with Maf recognition element arrays by surface plasmon resonance imaging technique. (2004)
  • Author(s): Kyo, M., et al.
  • Journal Title: Genes Cells 9 Pages: 153-164
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Transgenic rescue of GATA-1-deficient mice with GATA-1 lacking a FOG-1 association site phenocopies patients with X-linked thrombocytopenia. (2004)
  • Author(s): Shimizu, R., et al.
  • Journal Title: Blood 103 Pages: 2560-2567
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Role of Nrf2 in the regulation of CD36 and stress protein expression in murine macrophages : activation by oxidatively modified LDL and 4-hydroxynonenal. (2004)
  • Author(s): Ishii, T., et al.
  • Journal Title: Circulation Res. 94 Pages: 609-616
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Protection against electrophile and oxidant stress by induction of the phase 2 response : Fate of cysteines of the Keap1 sensor modified by inducers. (2004)
  • Author(s): Wakabayashi, N., et al.
  • Journal Title: Proc. Natl. Acad. Sci. USA 101 Pages: 2040-2045
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Scaffolding of Keap1 to the actin cytoskeleton controls the function of Nrf2 as key regulator of cytoprotective phase 2 genes. (2004)
  • Author(s): Kang, M.I., et al.
  • Journal Title: Proc. Natl. Acad. Sci. USA 101 Pages: 2046-2051
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Neurogenin3 delineates the earliest stages of spermatogenesis in the mouse testis. (2004)
  • Author(s): Yoshida, S., et al.
  • Journal Title: Dev. Biol. 269 Pages: 447-458
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Interleukin-6 and tumor necrosis factor-a in patients with obstructive sleep apnea-hypopnea syndrome. (2004)
  • Author(s): Imagawa, S., et al.
  • Journal Title: Respiration 71 Pages: 24-29
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Small Maf proteins are obligate transcriptional cofactors for normal keratinocyte differentiation in the Keap1-Nrf2 regulatory pathway. (2004)
  • Author(s): Motohashi, H., et al.
  • Journal Title: Proc. Natl. Acad. Sci. USA 101 Pages: 6379-6384
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Nrf2 deficiency improves autoimmune nephritis caused by the fas mutation lpr. (2004)
  • Author(s): Morito, N., et al.
  • Journal Title: Kidney Int. 65 Pages: 1703-1713
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A constitutively active arylhydrocarbon receptor induces growth inhibition of Jurkat T cells through changes in the expression of genes related to apoptosis and cell cycle arrest. (2004)
  • Author(s): Ito, T., et al.
  • Journal Title: J. Biol. Chem. 279 Pages: 25204-25210
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Activation of hepatic Nrf2 in vivo by acetaminophen in CD-1 Mice. (2004)
  • Author(s): Goldring, C.E.P., et al.
  • Journal Title: Hepatoloay 39 Pages: 1267-1276
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] In vivo and in vitro constant expression of GATA-4 in mouse postnatal Sertoli cells. (2004)
  • Author(s): Imai, T., et al.
  • Journal Title: Mol. Cell. Endocrinol. 214 Pages: 107-115
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Nrf2 deficiency causes tooth decolorization due to iron transport disorder in enamel organ. (2004)
  • Author(s): Yanagawa, T., et al.
  • Journal Title: Genes Cells 9 Pages: 641-651
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Redox-regulated turnover of Nrf2 is determined by at least two separate protein domains, the redox sensitive Neh2 degron and the redox-insensitive Neh6 degron. (2004)
  • Author(s): McMahon, M., et al.
  • Journal Title: J. Biol. Chem. 279 Pages: 31556-31567
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• [Journal Article] The transcriptional program of antibody class switching involves the repressor Bach2. (2004)
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  • Author(s): Takagi, Y., et al.
  • Journal Title: Biochem. Biophys. Res. Commun. 320 Pages: 62-69
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Oxidative stress sensor Keap1 functions as an adaptor for Cu13-based E3 ligase to regulate proteasomal degradation of Nrf2. (2004)
  • Author(s): Kobayashi, A., et al.
  • Journal Title: Mol. Cell. Biol. 24 Pages: 7310-7319
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Identification of polymorphisms in the promoter region of human NRF2 gene. (2004)
  • Author(s): Yamamoto, T., et al.
  • Journal Title: Biochem. Biophys. Res. Commun. 321 Pages: 72-79
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Do β-globin, GATA-1 or EpoR regulatory domains specifically mark erythroid progenitors in transgenic reporter mice? (2004)
  • Author(s): Suzuki, N., et al.
  • Journal Title: Blood 104 Pages: 2968-2969
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Multiple, distant Gata2 enhancers specify temporal and tissue-specific patterning in the developing urogenital system. (2004)
  • Author(s): Khandekar, M. J., et al.
  • Journal Title: Mot. Cell. Biol 24 Pages: 10263-10276
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Nrf2 is essential for the chemopreventive efficacy of oltipraz against urinary bladder carcinogenesis. (2004)
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  • Journal Title: Cancer Res. 64 Pages: 6124-6431
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Genetic ablation of Nrf2 enhances susceptibility to cigarette smoke-induced emphysema in mice. (2004)
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  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A GATA-specific inhibitor (K-7174) rescues anemia induced by IL-1β, TNF-α or L-NMMA. (2004)
  • Author(s): Imagawa, S., et al.
  • Journal Title: Blood 104 Pages: 4300-4307
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Transcription factor Nrf2 is essential for induction of NAD(P)H : quinone oxidoreductase 1, glutathione S-transferases, and glutamate cysteine ligase by broccoli seeds and isothiocyanates. (2004)
  • Author(s): McWalter, G.K., et al.
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  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Leukemogenesis caused by incapacitated GATA-1 function. (2004)
  • Author(s): Shimizu, R., et al.
  • Journal Title: Mol. Cell. Biol. 24 Pages: 10814-10825
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Transcription factor Nrf2 regulates inflammation by mediating the effect of 15-deoxy-D^<12,14>-prostaglandin J_2. (2004)
  • Author(s): Itoh, K., et al.
  • Journal Title: Mol. Cell. Biol. 24 Pages: 36-45
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Protection against electrophile and oxidant stress by induction of the phase 2 response : Fate of cysteines of the Keap1 sensor modified by inducers. (2004)
  • Author(s): Yoshida, S., et al.
  • Journal Title: Dev. Biol. 269 Pages: 447-458
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Small Maf proteins are obligate transcriptional cofactors for normal keratinocyte differentiation in the Keapl-Nrf2 regulatory pathway. (2004)
  • Author(s): Motohashi, H., et al.
  • Journal Title: Proc. Natl. Acad. Sci. USA 101 Pages: 6379-6384
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Activation of hepatic Nrf2 in vivo by acetaminophen in CD-1 Mice. (2004)
  • Author(s): Goldring, C.E.P., et al.
  • Journal Title: Hepatology 39 Pages: 1267-1276
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] MafT, a new member of the small Maf protein family in zebrafish. (2004)
  • Author(s): Takagi, Y., et al.
  • Journal Title: Biochem. Biophys. Res. Commum. 320 Pages: 62-69
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Oxidative stress sensor Keap1 functions as an adaptor for Cul3-based E3 ligase to regulate proteasomal degradation of Nrf2. (2004)
  • Author(s): Kobayashi, A., et al.
  • Journal Title: Mol. Cell. Biol. 24 Pages: 7310-7319
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Identification of polymorphisms in the promoter region of human NRF2 gene. (2004)
  • Author(s): Yamamoto, T., et al.
  • Journal Title: Biochem. Biophys. Res. Commum. 321 Pages: 72-79
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Do b-globin, GATA-1 or EpoR regulatory domains specifically mark erythroid progenitors in transgenic reporter mice? (2004)
  • Author(s): Suzuki, N., et al.
  • Journal Title: Blood 104 Pages: 2968-2969
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Multiple, distant Gata2 enhancers specify temporal and tissue-specific patterning in the developing urogenital system. (2004)
  • Author(s): Khandekar, M. J., et al.
  • Journal Title: Mol. Cell. Biol. 24 Pages: 10263-10276
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A GATA-specific inhibitor (K-7174) rescues anemia induced by IL-1b, TNF-a or L-NMMA. (2004)
  • Author(s): Imagawa, S., et al.
  • Journal Title: Blood 104 Pages: 4300-4307
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Transgenic rescue of GATA-1-deficient mice with GATA-1 lacking a FOG-1 association site phenocopies patients with X-linked thrombocytopenia. (2004)
  • Author(s): Shimizu, R., Ohneda, K., Engel, J.D., Trainor, C.D.
  • Journal Title: Blood 103 Pages: 2560-2567
• [Journal Article] Role of Nrf2 in the regulation of CD36 and stress protein expression in murine macrophages : activation by oxidatively modified LDL and 4-hydroxynonenal (2004)
  • Author(s): Ishii, T., Itoh, K., Ruiz, E., Leake, D.S., Unoki, H., Yamamoto, M., Mann, G.E.
  • Journal Title: Circulation 94 Pages: 609-616
• [Journal Article] Protection against electrophile and oxidant stress by induction of the phase 2 response : Fate of cysteines of the Keap1 sensor modified by inducers. (2004)
  • Author(s): Wakabayashi, N., Dinkova-Kostova, A.T.Holtzclaw, W.D., Kang, M-L, Kobayashi, A., Yamamoto, M., Kensler, T.W., Talalay, P.
  • Journal Title: Proc.Natl.Acad.Sci.USA 101 Pages: 2040-2045
• [Journal Article] Scaffolding of Keap1 to the actin cytoskeleton controls the function of Nrf2 as key regulator of cytoprotective phase 2 genes. (2004)
  • Author(s): Kang, M.I., Kobayashi, A., Wakabayashi, N., Kim, S.G., Yamamoto, M.
  • Journal Title: Proc.Natl.Acad.Sci.USA 101 Pages: 2046-2051
• [Journal Article] Neurogenin3 delineates the earliest stages of spermatogenesis in the mouse testis. (2004)
  • Author(s): Yoshida, S., Takakura, A., Ohbo, K., Abe, K., Wakabayashi, J., Yamamoto, M., Suda, T., Nabeshima, Y-i.
  • Journal Title: Dev.Biol. 269 Pages: 447-458
• [Journal Article] Interleukin-6 and tumor necrosis factor-a in patients with obstructive sleep apnea-hypopnea syndrome (2004)
  • Author(s): Imagawa, S., Yamaguchi, Y., Ogawa, K., Obara, N., Suzuki, N., Yamamoto, M., Nagasawa, T
  • Journal Title: Respiration 71 Pages: 24-29
• [Journal Article] Small Maf proteins are obligate transcriptional cofactors for normal keratinocyte differentiation in the Keap1-Nrf2 regulatory pathway. (2004)
  • Author(s): Motohashi, H., Katsuoka, F., Engel, J.D., Yamamoto, M.
  • Journal Title: Proc.Natl.Acad.Sci.USA 101 Pages: 6379-6384
• [Journal Article] Nrf2 deficiency improves autoimmune nephritis caused by the fas mutation lpr (2004)
  • Author(s): Morito, N., Yoh, K., Hirayama, A., Itoh, K., Nose, M., Koyama, A., Yamamoto, M.
  • Journal Title: Kidney Int. 65 Pages: 1703-1713
• [Journal Article] A constitutively active arylhydrocarbon receptor induces growth inhibition of Jurkat T cells through changes in the expression of genes related to apoptosis and cell cycle arrest. (2004)
  • Author(s): Ito, T., Tsukumo, S., Suzuki, N., Motohashi, H., Yamamoto, M., Fujii-Kuriyama, Y.
  • Journal Title: J.Biol.Chem. 279 Pages: 25204-25210
• [Journal Article] Activation of hepatic Nrf2 in vivo by acetaminophen in CD-1 Mice. (2004)
  • Author(s): Goldring, C.E.P., Kitteringham, N.R., Elsby, R., Randle, L.E., Clement, Y.N., Williams, D.P., McMahon, M., Hayes, J.D., Itoh, K., Yamamoto, M., Park, B.K.
  • Journal Title: Hepatology 39 Pages: 1267-1276
• [Journal Article] In vivo and in vitro constant expression of GATA-4 in mouse postnatal Sertoli cells. (2004)
  • Author(s): Imai, T., Kawai, Y., Tadokoro, Y., Yamamoto, M., Nishimune, Y., Yomogida, K.
  • Journal Title: Mol.Cell.Endocrinol. 214 Pages: 107-115
• [Journal Article] Nrf2 deficiency causes tooth decolourization due to iron transport disorder in enamel organ. (2004)
  • Author(s): Yanagawa, T., Itoh, K., Uwayama, J., Shibata, Y., Yamaguchi, A., Sano, T., Ishii, T., Yoshida, H., Yamamoto, M.
  • Journal Title: Genes Cells 9 Pages: 641-651
  • NAID: 120007131624
• [Journal Article] Redox-regulated turnover of Nrf2 is determined by at least two separate protein domains, the redox sensitive Neh2 degron and the redox-insensitive Neh6 degron. (2004)
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• [Journal Article] Identification of polymorphisms in the promoter region of the human NRF2 gene. (2004)
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• [Journal Article] Do b-globin, GATA-1 or EpoR regulatory domains specifically mark erythroid progenitors in transgenic reporter mice? (2004)
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• [Journal Article] Multiple, distant Gata2 enhancers specify temporal and tissue-specific patterning in the developing urogenital system. (2004)
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• [Journal Article] Nrf2 Is Essential for the Chemopreventive Efficacy of Oltipraz against Urinary Bladder Carcinogenesis. (2004)
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• [Journal Article] Aberrant iron accumulation and oxidized status of erythroid-specific δ-aminolevulinate synthase (ALAS2)-deficient definitive erythroblasts. (2003)
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• [Journal Article] A GATA-specific inhibitor (K-7174) rescues anemia induced by IL-1β, TNF-α or L-NMMA. (2003)
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• [Journal Article] Hematological aspects of a novel 9-aminoanthracycline, amrubicin. (2003)
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• [Journal Article] Small Maf compound mutants display CNS neuronal degeneration, aberrant transcription and Bach protein mislocalization coincident with myoclonus and abnormal startle response. (2003)
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• [Journal Article] Aberrant iron accumulation and oxidized status of erythroid-specific d-aminolevulinate synthase (ALAS2)-deficient definitive erythroblasts. (2003)
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• [Journal Article] Modulation of keap1 and nrf2-dependent gene expression by cancer chemopreventive dithiolethiones : IDENTIFICATION OF NOVEL GENE CLUSTERS. (2003)
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• [Journal Article] HLF (HIF-2a) is a key factor for pathological angiogenesis in proliferative retinopathy. (2003)
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• [Journal Article] Gene expression of detoxifying enzymes in AhR and Nrf2compound null mutant mouse. (2003)
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• [Journal Article] Self-association of Gata1 enhances transcriptional activity in vivo in zebrafish embryos. (2003)
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• [Journal Article] A GATA-specific inhibitor (K-7174) rescues anemia induced by IL-lb, TNF-a or L-NMMA. (2003)
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• [Journal Article] Hemoprotein Bach1 regulates enhancer availability of heme oxygenase-1 gene. (2002)
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• [Journal Article] A minigene containing four discrete cis elements recapitulates GATA-1 gene expression in vivo. (2002)
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  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Solution structure of the DNA-binding domain of MafG. (2002)
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• [Journal Article] Nrf2 transactivator-independent GSTP1-1 expression in GSTP1-1 positive' single cells inducible in female mouse liver by DEN : a preneoplastic character of possible initiated cells. (2002)
  • Author(s): Satoh, K., et al.
  • Journal Title: Carcinogenesis 23 Pages: 457-462
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A candidate erythroid embryonic/ fetal globin gene repressor contains a nuclear orphan receptor TR2/TR4 heterodimer. (2002)
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  • Journal Title: EMBOJ. 21 Pages: 3434-3442
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• [Journal Article] Identification of the interactive interface and phylogenic conservation of the Nrf2-Keapl system. (2002)
  • Author(s): Kobayashi, M., et al.
  • Journal Title: Genes Cells 7 Pages: 807-820
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] GATA-2 regulates cytokine-dependent growth of hematopoietic cells through accumulation of p21WAF1 and p27Kipl proteins. (2002)
  • Author(s): Ezoe, S., et al.
  • Journal Title: Blood 100 Pages: 3512-3520
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] High sensitivity of Nrf2 knockout mice to acetoaminophen hepatotoxicity associated with decreased expression of ARE-regulated drug metabolizing enzyme and antioxidant genes. (2001)
  • Author(s): Enomoto, A., et al.
  • Journal Title: Toxicol. Sci. 59 Pages: 169-177
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Stimulation of GATA-2 as a mechanism of hydrogen peroxide suppression in hypoxia-induced erythropoietin gene expression. (2001)
  • Author(s): Tabata, M., et al.
  • Journal Title: J. Cell. Physiol. 186 Pages: 260-267
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Sensitivity to carcinogenesis is increased and chemoprotective efficacy of enzyme inducers is lost in nrf2 transcription factor-deficient mice. (2001)
  • Author(s): Ramos-Gomez, M., et al.
  • Journal Title: Proc. Natl. Acad. Sci. USA 98 Pages: 3410-3415
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Role of Transcription factor Nrf2 in the induction of hepatic phase 2 and antioxidative enzymes in vivo by the cancer chemopreventive agent, 3H-1, 2-dithiole-3-thione. (2001)
  • Author(s): Kwak, M-K., et al.
  • Journal Title: Mol. Med. 7 Pages: 135-145
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Transcription factor BACH1 is recruited to nucleus by its novel alternative spliced isoform expressed in testis. (2001)
  • Author(s): Kanezaki, R., et al.
  • Journal Title: J. Biol. Chem. 276 Pages: 7278-7284
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The homeobox protein Six3 interacts with the Groucho corepressor and acts as a transcriptional repressor in eye and forebrain formation. (2001)
  • Author(s): Kobayashi, M., et al.
  • Journal Title: Dev. Biol. 232 Pages: 315-326
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Defective development of secretary neurons in the hypothalamus of Arnt2-knockout mice. (2001)
  • Author(s): Hosoya, T., et al.
  • Journal Title: Genes Cells 6 Pages: 361-374
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Function of GATA transcription factors in the induction of endothelial VCAM-1 by TNF-α. (2001)
  • Author(s): Umetani, M., et al.
  • Journal Title: Arterioscler. Thromb. Vasc. Biol. 21 Pages: 917-922
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Positive regulation by GATA-1 of GATA-1 gene hematopoietic regulatory domain in zebrafish embryos in vivo. (2001)
  • Author(s): Kobayashi, M., et al.
  • Journal Title: Development 128 Pages: 2341-2350
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Accelerated DNA adducts formation in the lung of the Nrf2 knockout mouse exposed to diesel exhaust. (2001)
  • Author(s): Aoki, Y., et al.
  • Journal Title: Toxicol. Appl. Pharmacol. 173 Pages: 154-160
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Hemin-induced activation of the Thioredoxin gene by Nrf2 : a differential regulation of the antioxidant responsive element (ARE) by switch of its binding factors. (2001)
  • Author(s): Kim, Y-C., et al.
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  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Heme mediates de-repression of Maf recognition element through direct binding to transcription factor Bachl. (2001)
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  • Journal Title: EMBO J. 20 Pages: 2835-2843
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• [Journal Article] Nrf2 deficient mouse : a novel model for lupus nephritis. (2001)
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  • Journal Title: Kidney Int. 60 Pages: 1343-1353
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Two domains of Nrf2 cooperatively bind CBP (CREB binding protein) and synergistically activate transcription. (2001)
  • Author(s): Katoh, Y., et al.
  • Journal Title: Genes Cells 6 Pages: 857-868
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• [Journal Article] In vivo requirements for functional GATA-1 domains during primitive and definitive erythropoiesis. (2001)
  • Author(s): Shimizu, R., et al.
  • Journal Title: EMBO J. 20 Pages: 5250-5260
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• [Journal Article] The promoter of mouse transcription repressor bach1 is regulated by Sp1 and transactivated by Bach1. (2001)
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  • Journal Title: J. Biochem. 130 Pages: 385-392
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• [Journal Article] The Cap' n' Collar basic leucine zipper transcription factor Nrf2 controls both constitutive and inducible expression of intestinal detoxification and glutathione biosynthetic enzymes. (2001)
  • Author(s): McMahon, M., et al.
  • Journal Title: Cancer Res. 61 Pages: 3299-3307
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• [Journal Article] Levels of vascular endothelial growth factor are elevated in patients with obstructive sleep apnea-hypopnea syndrome. (2001)
  • Author(s): Imagawa, S., et al.
  • Journal Title: Blood 98 Pages: 1255-1257
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Role of phase 2 enzyme induction in chemoprotection by dithiolethiones. (2001)
  • Author(s): Kwak, M.K., et al.
  • Journal Title: Mutat Res. 481 Pages: 305-315
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• [Journal Article] Stepwise divergence of primitive and definitive hematopoietic cell and endothelial cell lineages. (2001)
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  • Journal Title: Genes Cells 6 Pages: 1113-1127
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Transgenic overexpression of MafK suppresses T cell proliferation and function in vivo. (2001)
  • Author(s): Yoh, K., et al.
  • Journal Title: Genes Cells 6 Pages: 1055-1066
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Function of GATA transcription factors in the induction of endothelial VCAM-1 by TNF-a. (2001)
  • Author(s): Umetani, M., et al.
  • Journal Title: Arterioscler. Thromb. Vasc. Biol. 21 Pages: 917-922
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Heme mediates de-repression of Maf recognition element through direct binding to transcription factor Bach1. (2001)
  • Author(s): Ogawa, K., et al.
  • Journal Title: EMBO J. 20 Pages: 2835-2843
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A GATA box in the GATA-1 gene hematopoietic enhancer is critical element in the network of GATA factors and sites that regulate this gene. (2000)
  • Author(s): Nishimura, S., et al.
  • Journal Title: Mol. Cell. Biol 20 Pages: 713-723
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Identification of human GATA-2 gene distal IS exon and its expression in hematopoietic stem cell fractions. (2000)
  • Author(s): Pan, X., et al.
  • Journal Title: J. Biochem 127 Pages: 105-112
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A combinatorial code for gene expression generated by transcription factor Bach2 and MAZR (MAZ-related factor) through BTB/POZ domain. (2000)
  • Author(s): Kobayashi, A., et al.
  • Journal Title: Mol. Cell. Biol. 20 Pages: 1733-1746
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Perinatal synthetic lethality and hematopoietic defects in compound mafG : : mafKmutant mice. (2000)
  • Author(s): Onodera, K., et al.
  • Journal Title: EMBO J. 19 Pages: 2980-1746
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• [Journal Article] One enhancer mediates mafK transcriptional activation in both hematopoietic and cardiac muscle cells. (2000)
  • Author(s): Katsuoka, F., et al.
  • Journal Title: EMBO J. 19 Pages: 2980-2991
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] GATA-1 blocks IL-6-induced macrophage differentiation and apoptosis through the sustained expression of cyclinDlandBcl-2inamurinemyeloidcell line MI. (2000)
  • Author(s): Tanaka, H., et al.
  • Journal Title: Blood 95 Pages: 1264-1273
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Induction of murine intestinal and hepatic peroxiredoxin MSP23 by dietary butylated hydroxyanisole. (2000)
  • Author(s): Ishii, T., et al.
  • Journal Title: Carcinogenesis 21 Pages: 1013-1016
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Eosinophil-specific regulation of gp91phox gene expression by transcription factors GATA-1 and GATA-2. (2000)
  • Author(s): Yang, D., et al.
  • Journal Title: J. Biol. Chem. 275 Pages: 9425-9432
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• [Journal Article] Oxidative stress abolishes leptomycine B-sensitive nuclear export of transcription repressor Bach2 that counteracts activation of Maf recognition element. (2000)
  • Author(s): Hoshino, H., et al.
  • Journal Title: J. Biol. Chem. 275 Pages: 15370-15376
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Transcription factor Nrf2 coordinately regulates a group of oxidative stress-inducible genes in macrophages. (2000)
  • Author(s): Ishii, T., et al.
  • Journal Title: J. Biol. Chem. 275 Pages: 16023-16029
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• [Journal Article] GATA factor transgenes under GATA-1 locus control rescue germ line GATA-1 mutant deficiencies. (2000)
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  • Journal Title: Blood 96 Pages: 910-916
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• [Journal Article] Cloning of a coproporphyrinogen oxidase promoter regulatory element binding protein. (2000)
  • Author(s): Takahashi, S-I., et al.
  • Journal Title: Biochem. Biophys. Res. Commun. 273 Pages: 596-602
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Cloning and expression of human B cell-specific transcription factor BACH2 mapped to chromosome 6p15. (2000)
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  • Journal Title: Oncogene 19 Pages: 3739-3749
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The Nrf2 transcription factor contributes both to the basal expression of glutathione S-transferases in mouse liver and to their induction by the chemopreventive synthetic antioxidants, butylated hydroxyanisole and ethoxyquin. (2000)
  • Author(s): Hayes, J.D., et al.
  • Journal Title: Biochem. Soc. Trans. 28 Pages: 33-41
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] GATA2 is required for the generation of V2 interneurons. (2000)
  • Author(s): Zhou, Y., et al.
  • Journal Title: Development 127 Pages: 3829-3838
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Biologic significance of GATA-1 activities in Ras-mediated megakaryocytic differentiation of hematopoietic cell lines. (2000)
  • Author(s): Matsumura, I., et al.
  • Journal Title: Blood 96 Pages: 2440-2450
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• [Journal Article] N(G)-monomethyl-L-arginine inhibits erythropoietin gene expression by stimulating GATA-2. (2000)
  • Author(s): Tarumoto, T., et al.
  • Journal Title: Blood 96 Pages: 1716-1722
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Functional characterization of the two alternative promoters of human p45 NF-E2 gene. (2000)
  • Author(s): Toki, T., et al.
  • Journal Title: Exp. Hematol. 28 Pages: 1113-1119
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A novel cis-acting element regulates HES-1 gene expression in P19 embryonal carcinoma cells treated with retinoic acid. (2000)
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  • Journal Title: J. Biochem. 128 Pages: 1087-1095
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Expression of three zebrafish Six3 genes in cranial sensory placodes and the developing somites. (2000)
  • Author(s): Kobayashi, M., et al.
  • Journal Title: Mech. Dev. 98 Pages: 151-155
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Positive or negative MARE-dependent transcriptional regulation is determined by the abundance of small Maf proteins. (2000)
  • Author(s): Motohashi, H., et al.
  • Journal Title: Cell 103 Pages: 865-875
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A GATA box in the GATA-1 gene hematopoietic enhancer is critical element in the network of GATA factors and sites that regulate this gene. (2000)
  • Author(s): Nishimura, S., et al.
  • Journal Title: Mol. Cell. Biol. 20 Pages: 713-723
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Identification of human GATA-2 gene distal IS exon and its expression in hematopoietic stem cell fractions. (2000)
  • Author(s): Pan, X., et al.
  • Journal Title: J. Biochem. 127 Pages: 105-112
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Perinatal synthetic lethality and hematopoietic defects in compound mafG : mafK mutant mice. (2000)
  • Author(s): Onodera, K., et al.
  • Journal Title: EMBO J. 19 Pages: 1335-1345
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] GATA-1 blocks IL-6-induced macrophage differentiation and apoptosis through the sustained expression of cyclin Dl and Bc1-2 in a murine myeloid cell line Ml. (2000)
  • Author(s): Tanaka, H., et al.
  • Journal Title: Blood 95 Pages: 1264-1273
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Transgenic expression of Bach1 transcription factor results in megakaryocytic impairment.
  • Author(s): Toki, T., et al.
  • Journal Title: Blood (印刷中)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Essential role of synoviolin in embryogenesis.
  • Author(s): Yagishita, N., et al.
  • Journal Title: J. Biol. Chem. (印刷中)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Restricted expression of constitutively active-aryl hydrocarbon receptor in T lineage cells causes thymus involution and suppresses immunization-induced splenocyte increase.
  • Author(s): Nohara, K., et al.
  • Journal Title: J. Immunol. (印刷中)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Pi-class glutathione S-transferase genes are regulated by Nrf2 through an evolutionarily conserved regulatory element in zebrafish.
  • Author(s): Suzuki, T., et al.
  • Journal Title: Biochem. J. (印刷中)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] UVA irradiation induces Nrf2 activation in dermal fibroblasts : Protective role in UVA-induced apoptosis.
  • Author(s): Hirota, A., et al.
  • Journal Title: Invest. Dermatol. (印刷中)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The distal sequence element of the selenocysteine tRNA gene is a tissue dependant enhancer essential for mouse embryogenesis.
  • Author(s): Kelly, V.P., et al.
  • Journal Title: Mol. Cell. Biol. (印刷中)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] GATA transcription factors inhibit cytokine-dependent growth and survival of a hematopoietic cell line through the inhibition of STAT3 activity.
  • Author(s): Ezoe, S., et al.
  • Journal Title: J. Biol. Chem. (印刷中)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Role of 15-deoxyΔ^<12-14> Prostaglandin J_2 and Nrf2 Pathways in Protection against Acute Lung Injury.
  • Author(s): Mochizuki, M., et al.
  • Journal Title: Am. J. Res. Cri. Care Med. (印刷中)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Increased dose of Runx1/AML1 acts as a positive modulator of myeloid leukemogenesis in BXH2 mice.
  • Author(s): Yanagida, M., et al.
  • Journal Title: Oncogene (印刷中)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Rapid turnover of GATA-2 via ubiquitin-proteasome protein degradation pathway.
  • Author(s): Minegishi, N., et al.
  • Journal Title: Genes Cells (印刷中)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] MafA is a key regulator of glucose-stimulated insulin secretion.
  • Author(s): Zhang, C., et al.
  • Journal Title: Mol. Cell. Biol. (印刷中)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Transgenic expression of Bach1 transcription factor results in megakaryocytic impairment.
  • Author(s): Toki, T., et al.
  • Journal Title: Blood (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Essential role of synoviolin in embryogenesis.
  • Author(s): Yagishita, N., et al.
  • Journal Title: J. Biol. Chem. (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Restricted expression of constitutively active-aryl hydrocarbon receptor in T lineage cells causes thymus involution and suppresses immunization-induced splenocyte increase.
  • Author(s): Nohara, K., et al.
  • Journal Title: J. Immunol. (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Pi-class glutathione S-transferase genes are regulated by Nrf2 through an evolutionarily conserved regulatory element in zebrafish.
  • Author(s): Suzuki, T., et al.
  • Journal Title: Biochem. J. (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] UVA irradiation induces Nrf2 activation in dermal fibroblasts : Protective role in UVA-induced apoptosis.
  • Author(s): Hirota, A., et al.
  • Journal Title: Invest. Dermatol. (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The distal sequence element of the selenocysteine tRNA gene is a tissue dependant enhancer essential for mouse embryogenesis.
  • Author(s): Kelly, V.P., et al.
  • Journal Title: Mol. Cell. Biol. (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] GATA transcription factors inhibit cytokine-dependent growth and survival of a hematopoietic cell line through the inhibition of STAT3 activity.
  • Author(s): Ezoe, S., et al.
  • Journal Title: J. Biol. Chem. (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Role of 15-deoxyD^<12-14> Prostaglandin J2 and Nrf2 Pathways in Protection against Acute Lung Injury.
  • Author(s): Mochizuki, M., et al.
  • Journal Title: Am. J. Res. Cri. Care Med. (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Increased dose of Runxl/AML1 acts as a positive modulator of myeloid leukemogenesis in BXH2 mice.
  • Author(s): Yanagida, M., et al.
  • Journal Title: Oncogene (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Rapid turnover of GATA-2 via ubiquitin-proteasome protein degradation pathway.
  • Author(s): Minegishi, N., et al.
  • Journal Title: Genes Cells (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] MafA is a key regulator of glucose-stimulated insulin secretion.
  • Author(s): Zhang, C., et al.
  • Journal Title: Mol. Cell. Biol. (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Transgenic expression of Bach1 transcription factor results in megakaryocytic impairment.
  • Author(s): Toki, T., Katsuoka, F., Kanezaki, R., Xu, G., Kurotaki, H., Sun, J., Kamio, T., Watanabe, S., Tandai, S., Terui, K., Yagihashi, S., Komatsu, N., Igarashi, K., Yamamoto, M., Ito, E.
  • Journal Title: Blood (印刷中)
• [Publications] Katsuoka, F.: "Small Maf compound mutants display CNS neuronal degeneration, aberrant transcription and Bach protein mislocalization coincident with myoclonus and abnormal startle response"Mol.Cell.Biol.. 23. 1163-1174 (2003)
• [Publications] Morita, M.: "HLF(HIF-2a) is a key factor for pathological angiogenesis in proliferative retinopathy"EMBO J.. 22. 1134-1146 (2003)
• [Publications] Moriguchi, T.: "Distinct specificity of xenobiotic response in AhR-humanized model mouse"Proc.Natl.Acad.Sci.USA. 100. 5652-5657 (2003)
• [Publications] Minegishi, N.: "Expression and domain-specific function of GATA-2 during differentiation of the hematopoietic precursor cells in midgestation mouse embryos"Blood. 102. 896-905 (2003)
• [Publications] Wakabayashi, J.: "GATA-1 testis activation region is essential for Sertoli cell-specific expression of GATA-1 gene in transgenic mouse"Genes Cells. 8. 619-630 (2003)
• [Publications] Xu, G, Nagano, M: "Frequent mutations in the GATA-1 gene in the transient myeloproliferative disorder of Down' s syndrome"Blood. 102. 2960-2968 (2003)
• [Publications] Suzuki, N.: "Identification and characterization of two types of erythroid progenitors that express GATA-1 at distinct levels"Blood. 102. 3575-3583 (2003)
• [Publications] Nishikawa, K.: "Self-association of Gata1 enhances transcriptional activity in vivo in zebrafish embryos"Mol.Cell.Biol.. 23. 8295-8305 (2003)
• [Publications] Wakabayashi, N.: "Keap1-null mutation leads to postnatal lethality due to constitutive Nrf2 activation"Nature Genetics. 35. 238-245 (2003)
• [Publications] Shimizu, R.: "Transgenic rescue of GATA-1-deficient mice with GATA-1 lacking a FOG-1 association site phenocopies patients with X-linked thrombocytopenia"Blood. (In press). (2003)