2003 年度実績報告書

GATA転写因子群による造血細胞の細胞周期制御に関する解析

研究課題

研究課題/領域番号	14570978
研究機関	大阪大学
研究代表者	松村到大阪大学, 医学系研究科, 助教授 (00294083)
研究分担者	柴山浩彦大阪大学, 医学系研究科, 助手 (60346202) 水木満佐央大阪大学, 医学系研究科, 講師 (80283761) 金倉譲大阪大学, 医学系研究科, 教授 (20177489)
キーワード	GATA-1 / GATA-2 / 造血幹細胞 / c-myc / p21WAF1 / p27Kip1 / STAT3 / Ras
研究概要	1.GATA-2による細胞周期制御 (1)4-hydroxy tamoxifen(4-HT)によって活性が誘導されるGATA-2とエストロゲン受容体とのキメラ分子GATA-2/ERTを、IL-3依存性細胞株Ba/F3や正常造血幹/前駆細胞に導入したところ、いずれの細胞のサイトカイン依存性増殖も4-HTにより完全に抑制された。 (2)GATA-2による増殖抑制の際には、Ba/F3、正常造血細胞のいずれにおいてもc-myc、CDK4のmRNAの発現が早期より抑制され、p21^<WAF1>、p27^<KIP1>蛋白の増加が認められた。 (3)p21^<WAF1>、p27^<KIP1>蛋白の増加の原因として、これらの蛋白のユビキチン/プロテアソーム系を介する分解に関わるc-mycの標的分子Cul1の発現低下が認められた。 (4)造血幹細胞を各種サイトカイン存在下で培養し、細胞周期に導入するとGATA-2の発現が低下した。以上の結果から、造血幹細胞に発現するGATA-2は、c-mycの発現を抑制し、造血幹細胞の休止期の維持に寄与すると考えられた。 2.GATA-1による細胞内シグナル伝達の制御 (1)GATA-1/ERTを導入したBa/F3細胞において、GATA-1はN-zinc fingerを介してSTAT3と直接結合し、STAT3のDNA結合能を抑制した。 (3)GATA-1はBa/F3細胞において活性型H-RasG12VのよるMEKK1の活性化を抑制し、活性型H-RasG12V依存性の細胞増殖・生存を阻害した。これらの結果から、GATA-1はSTAT3やRas/MAPKの経路を抑制し、造血細胞のサイトカイン依存性の増殖・生存を抑制すると考えられた。

研究成果

(22件)

すべてその他

すべて文献書誌 (22件)

[文献書誌] Kawasaki A, et al.: "Opposing effects of PML and PML/RAR α on STAT3 activity"Blood. 101. 3668-3673 (2003)
[文献書誌] Mizuki M, et al.: "Suppression of myeloid transcription factors and induction of STAT response genes by AML-specific Flt3 mutations"Blood. 101. 3164-3173 (2003)
[文献書誌] Kataoka Y, et al.: "Reciprocal inhibition between MyoD and STAT3 in the regulation of growth and differentiation of myoblasts"J.BIol.Chem.. 278. 44178-44187 (2003)
[文献書誌] Saeki Y, et al.: "Enhanced production of osteopontin in multiple myeloma : clinical and pathogenicimplications"Br.J.Haematol.. 123. 263-270 (2003)
[文献書誌] Zhang X, et al.: "Constitutively activated Rho GTPases regulate the growth and morphology of hairy cellleukemia (HCL) cells"Int.J.Hematology. 77. 263-270 (2003)
[文献書誌] Takakuwa T, et al.: "Establishment and characterization of unique cell lines derived from pyothorax-associated lymphoma which develops in long-standing pyothorax and is stronglyassociated with Epstein-Barr virus infection"Cancer Sci.. 94. 858-863 (2003)
[文献書誌] Matsumura I, et al.: "Molecular mechanisms of E2F1- and c-Myc-enhanced apoptosis"Rec.Res.Dev.in Mol.& Cell.Biol.. 4. 311-324 (2003)
[文献書誌] Matsumura I, et al.: "Roles for E2F1 and c-Myc in the regulation of cell growth and survival"Cell Cycle. 2. 333-338 (2003)
[文献書誌] Mizuki M, et al.: "Constitutive active receptor tyrosine kinase in hematological neoplasia"Rec.Res.Dev.in Mol.& Cell.Biol.. 4. 85-100 (2003)
[文献書誌] Mizuki M, et al.: "Oncogenic receptor tyrosine kinase in leukemia"Cellular and Molecular Biology. 49. 907-922 (2003)
[文献書誌] Matsumura I, et al.: "Cell cycle regulation in hematopoietic stem cells"Res.Adv.in Blood. 2. 39-49 (2003)
[文献書誌] Okawa Y, et al.: "Purification of N-terminally truncated histone H2A-monoubiquitin conjugates fromleukemic cell nuclei : probable proteolytic products of ubiquitinated H2A"Int.J.Biochem.Cell Biol.. 35. 1588-1600 (2003)
[文献書誌] Yamanishi H, et al.: "Total iron-binding capacity calculated from serum transferrin concentration or serumiron concentration and unsaturated iron-binding capacity"Clin.Chem.. 49. 175-178 (2003)
[文献書誌] Yamanishi H, et al.: "Modification of the colorimetric assay for serum unsaturated iron-binding capacity"Clin.Chem.. 49. 1023-1025 (2003)
[文献書誌] Kimura S, et al.: "Enzymatic assay for determination of bicarbonate ion in plasma using urea amidolyase"Clin, Chim.Acta.. 328. 179-184 (2003)
[文献書誌] Kimura S, et al.: "New enzymatic assay for serum urea nitrogen using urea amidolyase"J.Clin.Lab.Anal.. 17. 52-56 (2003)
[文献書誌] Kabutomori O, et al.: "Marked decreases of total and immature reticulocytes in myelodysplastic syndromeamong patients with pancytopenia"Acta Haematol.. 109. 212-213 (2003)
[文献書誌] Kabutomori O, et al.: "Incorrect measurement of leukocyte counts in post-bone marrow transplantation (P-BMT) patients"Ann.Hematol.. 82. 529-530 (2003)
[文献書誌] Ueda Y, et al.: "New homogeneous HDL-cholesterol assay without the influence of high TG sample using the selective detergent to lipoproteins"J Clin Lab Anal.. 17. 201-208 (2003)
[文献書誌] Tanaka S, et al.: "Autoantibodies against muscarinic cholinergic receptor in chronic fatigue syndrome"Int.J.Mol.Med.. 12. 225-230 (2003)
[文献書誌] Shibayama H, et al.: "Identification of a cytokine-induced antiapoptotic molecule Anamorsin essential for definitive hematopoiesis"J.Exp.Med.. 199. 581-592 (2004)
[文献書誌] Ezoe S, et al.: "Roles for CDK inhibtors in hematopoietic system"Cell Cycle. (in press). (2004)

2003 年度 実績報告書

GATA転写因子群による造血細胞の細胞周期制御に関する解析

研究代表者

松村 到 大阪大学, 医学系研究科, 助教授 (00294083)

研究成果

[文献書誌] Kawasaki A, et al.: "Opposing effects of PML and PML/RAR α on STAT3 activity"Blood. 101. 3668-3673 (2003)

[文献書誌] Mizuki M, et al.: "Suppression of myeloid transcription factors and induction of STAT response genes by AML-specific Flt3 mutations"Blood. 101. 3164-3173 (2003)

[文献書誌] Kataoka Y, et al.: "Reciprocal inhibition between MyoD and STAT3 in the regulation of growth and differentiation of myoblasts"J.BIol.Chem.. 278. 44178-44187 (2003)

[文献書誌] Saeki Y, et al.: "Enhanced production of osteopontin in multiple myeloma : clinical and pathogenicimplications"Br.J.Haematol.. 123. 263-270 (2003)

[文献書誌] Zhang X, et al.: "Constitutively activated Rho GTPases regulate the growth and morphology of hairy cellleukemia (HCL) cells"Int.J.Hematology. 77. 263-270 (2003)

[文献書誌] Takakuwa T, et al.: "Establishment and characterization of unique cell lines derived from pyothorax-associated lymphoma which develops in long-standing pyothorax and is stronglyassociated with Epstein-Barr virus infection"Cancer Sci.. 94. 858-863 (2003)

[文献書誌] Matsumura I, et al.: "Molecular mechanisms of E2F1- and c-Myc-enhanced apoptosis"Rec.Res.Dev.in Mol.& Cell.Biol.. 4. 311-324 (2003)

[文献書誌] Matsumura I, et al.: "Roles for E2F1 and c-Myc in the regulation of cell growth and survival"Cell Cycle. 2. 333-338 (2003)

[文献書誌] Mizuki M, et al.: "Constitutive active receptor tyrosine kinase in hematological neoplasia"Rec.Res.Dev.in Mol.& Cell.Biol.. 4. 85-100 (2003)

[文献書誌] Mizuki M, et al.: "Oncogenic receptor tyrosine kinase in leukemia"Cellular and Molecular Biology. 49. 907-922 (2003)

[文献書誌] Matsumura I, et al.: "Cell cycle regulation in hematopoietic stem cells"Res.Adv.in Blood. 2. 39-49 (2003)

[文献書誌] Okawa Y, et al.: "Purification of N-terminally truncated histone H2A-monoubiquitin conjugates fromleukemic cell nuclei : probable proteolytic products of ubiquitinated H2A"Int.J.Biochem.Cell Biol.. 35. 1588-1600 (2003)

[文献書誌] Yamanishi H, et al.: "Total iron-binding capacity calculated from serum transferrin concentration or serumiron concentration and unsaturated iron-binding capacity"Clin.Chem.. 49. 175-178 (2003)

[文献書誌] Yamanishi H, et al.: "Modification of the colorimetric assay for serum unsaturated iron-binding capacity"Clin.Chem.. 49. 1023-1025 (2003)

[文献書誌] Kimura S, et al.: "Enzymatic assay for determination of bicarbonate ion in plasma using urea amidolyase"Clin, Chim.Acta.. 328. 179-184 (2003)

[文献書誌] Kimura S, et al.: "New enzymatic assay for serum urea nitrogen using urea amidolyase"J.Clin.Lab.Anal.. 17. 52-56 (2003)

[文献書誌] Kabutomori O, et al.: "Marked decreases of total and immature reticulocytes in myelodysplastic syndromeamong patients with pancytopenia"Acta Haematol.. 109. 212-213 (2003)

[文献書誌] Kabutomori O, et al.: "Incorrect measurement of leukocyte counts in post-bone marrow transplantation (P-BMT) patients"Ann.Hematol.. 82. 529-530 (2003)

[文献書誌] Ueda Y, et al.: "New homogeneous HDL-cholesterol assay without the influence of high TG sample using the selective detergent to lipoproteins"J Clin Lab Anal.. 17. 201-208 (2003)

[文献書誌] Tanaka S, et al.: "Autoantibodies against muscarinic cholinergic receptor in chronic fatigue syndrome"Int.J.Mol.Med.. 12. 225-230 (2003)

[文献書誌] Shibayama H, et al.: "Identification of a cytokine-induced antiapoptotic molecule Anamorsin essential for definitive hematopoiesis"J.Exp.Med.. 199. 581-592 (2004)

[文献書誌] Ezoe S, et al.: "Roles for CDK inhibtors in hematopoietic system"Cell Cycle. (in press). (2004)

2003 年度実績報告書

松村到大阪大学, 医学系研究科, 助教授 (00294083)