2001 Fiscal Year Annual Research Report

遺伝性高発癌症候群の分子病態の解析および遺伝子治療の基礎的研究

Research Project

Project/Area Number	12670743
Research Institution	GIFU UNIVERSITY
Principal Investigator	金子英雄岐阜大学, 医学部・附属病院, 講師 (80293554)
Co-Investigator(Kenkyū-buntansha)	深尾敏幸岐阜大学, 医学部・附属病院, 講師 (70260578)
Keywords	BLM / ATM / ATM Kinase活性 / リン酸化 / telomerase / SUMO-1
Research Abstract	1)ATMとBLMの会合前年度までにATMとBLMが物理的に会合することを明らかにしてきたが、さらに機能的な会合について解析した。In vitro kinase assayを用いてATMがBLMをリン酸化する部位を検討した。ATMはBLMのN末の断片をリン酸化した。また、BLMのリン酸化はradiationにより誘導され、G2-M期の間におこる。Bloom syndrome由来の細胞株では、radiationによるATM kinase活性の経時的な活性の変化に異常がみられた。以上より、BLMはATMの上流と下流に位置することが示唆された。 2)ATM-/-,BLM-/-のダブルノックアウト細胞株の作製 ATMとBLMの会合がin vivoでどのような表現型を有するか検討するため、chicken DT-40細胞を用いてATM-/-,BLM-/-のダブルノックアウト細胞株の作製した。現在、その表現型をシングルノックアウト細胞株と比較し解析中である。 3)Bloom syndrome細胞にみられるtelomerase活性 BLMタンパクは一部のtelomereに局在していることが報告されている。そこで、BS患者由来の細胞株、またはB細胞リンパ腫でtelomerase活性をしらべたところ、その活性はcontrol細胞株とほぼ、同様に認められた。BLMは少なくともtelomeraseの主要な調節因子ではないと考えられた。 4)BLMはSUMO-1と会合し核内に局在する。 BLMをGFPとの融合ベクターを用いて強制発現させると核内にdot状に局在する。同時に、SUMO-1の抗体で染色すると、BLMとSUMO-1がco-localizeすることが明らかになった。BLMがSUMO-1と会合するにはBLMの238-586番目のアミノ酸が必要であり、この会合はBLMが核内にdot状に局在するのに必要なことを明らかにした。

Research Products

(16 results)

All Other

All Publications (16 results)

[Publications] Matsui E., et al.: "Reduced IFN-gamma production in response to IL-12 stimulation and/or reduced IL-12 production in atopic patients"Clin.Exp.Allergy. 30. 1250-1256 (2000)
[Publications] Fukao T., et al.: "Immunoblot analysis for laboratory diagnosis of ataxia-telangiectasia : Use of Epstein-Barr virus-transformed or phytohemagglutinin-stimulated lymphoblasts for detection of ATM protein."J.InVest.Allergol.Clin.Immunol.. 10. 36-40 (2000)
[Publications] Hayakawa S., et al.: "Characterization of the nuclear localization signal in the DNA helicase responsible for Bloom syndrome"Int.J.Mol.Med.. 5. 477-484 (2000)
[Publications] Kaneko H., et al.: "Long-term study of a female hyper IgM immunodeficiency"Exp.Clin.Immuogeretics. 17. 173-178 (2000)
[Publications] Kondo N: "Role of IL-12 receptor β2 mutations in the development of atopy"ACI International supplement. 1. 92-94 (2000)
[Publications] Terada T: "Fate of the mutated IgG2 haevy chain. : lack of expression of mutated membrane-bound IgG2 on the B cell surface in selective IgG2 deficiency"Int.Immunol.. 13. 249-256 (2001)
[Publications] Kaneko H., et al.: "Telomerase activity in cell lines and lymphoma originating from Bloom syndrome"Leukemia Lymphoma. 42. 757-760 (2001)
[Publications] Kondo N., et al.: "Reduced interferon-γ production and mutations of the IL-12 receptor β2 chain gene in atopic subjects"Int.Arch.Allergy.Immunol.. 124. 117-120 (2001)
[Publications] Inoue R., et al.: "Identification of beta-lactoglobulin-derived peptides and class II HLA molecules recognized by T cells from patients with milk allergy"Clin.Exp.Allergy. 31. 1126-34 (2001)
[Publications] Shikano H., et al.: "IFN-γ production in response to IL-18 or IL-12 stimulation by peripheral blood mononuclear cells of atopic patients"Clin.Exp.Allergy. 31. 1263-70 (2001)
[Publications] Kaneko H., et al: "Long-term duration of reduced serum complement level following burn injury"J.Investg.Allergol.Clin.Immunol.. 11. 303-304 (2001)
[Publications] Kondo N., et al.: "Atopy and mutations of IL-12 receptor β2 chain gene"Clin.Exp.Allergy. 31. 1189-93 (2001)
[Publications] Terada T., et al.: "Analysis of IgG subclass deficiency. : First reported case of IgG2,IgG4 and IgA deficiency caused by deletion of Cα1,ψCγ1,Cγ2,Cγ4 and Cεin a Mongoloid patient"J.Allergy Clin.Immunol.. 108. 602-606 (2001)
[Publications] Suzuki H., et al.: "The N-terminal region of BLM is required for the formation of dots/rod-like structure which are associated with SUMO-1"Biochem.Biophys.Res.Commun.. 286. 322-327 (2001)
[Publications] Kaneko H., et al.: "Detection of the genes induced in activated lymphocytes by modified differential display"J.Investig.Allergol.Clin.Immunol.. (in press). (2002)
[Publications] Watanabe M., et al.: "Predominant expression of 950delCAG of IL-18R alpha chain cDNA is associated with reduced IFN-gamma production and high serum IgE level in atopic patients"J.Allergy Clin.Immunol.. (in press). (2002)

2001 Fiscal Year Annual Research Report

遺伝性高発癌症候群の分子病態の解析および遺伝子治療の基礎的研究

Principal Investigator

金子 英雄 岐阜大学, 医学部・附属病院, 講師 (80293554)

Research Products

[Publications] Matsui E., et al.: "Reduced IFN-gamma production in response to IL-12 stimulation and/or reduced IL-12 production in atopic patients"Clin.Exp.Allergy. 30. 1250-1256 (2000)

[Publications] Fukao T., et al.: "Immunoblot analysis for laboratory diagnosis of ataxia-telangiectasia : Use of Epstein-Barr virus-transformed or phytohemagglutinin-stimulated lymphoblasts for detection of ATM protein."J.InVest.Allergol.Clin.Immunol.. 10. 36-40 (2000)

[Publications] Hayakawa S., et al.: "Characterization of the nuclear localization signal in the DNA helicase responsible for Bloom syndrome"Int.J.Mol.Med.. 5. 477-484 (2000)

[Publications] Kaneko H., et al.: "Long-term study of a female hyper IgM immunodeficiency"Exp.Clin.Immuogeretics. 17. 173-178 (2000)

[Publications] Kondo N: "Role of IL-12 receptor β2 mutations in the development of atopy"ACI International supplement. 1. 92-94 (2000)

[Publications] Terada T: "Fate of the mutated IgG2 haevy chain. : lack of expression of mutated membrane-bound IgG2 on the B cell surface in selective IgG2 deficiency"Int.Immunol.. 13. 249-256 (2001)

[Publications] Kaneko H., et al.: "Telomerase activity in cell lines and lymphoma originating from Bloom syndrome"Leukemia Lymphoma. 42. 757-760 (2001)

[Publications] Kondo N., et al.: "Reduced interferon-γ production and mutations of the IL-12 receptor β2 chain gene in atopic subjects"Int.Arch.Allergy.Immunol.. 124. 117-120 (2001)

[Publications] Inoue R., et al.: "Identification of beta-lactoglobulin-derived peptides and class II HLA molecules recognized by T cells from patients with milk allergy"Clin.Exp.Allergy. 31. 1126-34 (2001)

[Publications] Shikano H., et al.: "IFN-γ production in response to IL-18 or IL-12 stimulation by peripheral blood mononuclear cells of atopic patients"Clin.Exp.Allergy. 31. 1263-70 (2001)

[Publications] Kaneko H., et al: "Long-term duration of reduced serum complement level following burn injury"J.Investg.Allergol.Clin.Immunol.. 11. 303-304 (2001)

[Publications] Kondo N., et al.: "Atopy and mutations of IL-12 receptor β2 chain gene"Clin.Exp.Allergy. 31. 1189-93 (2001)

[Publications] Terada T., et al.: "Analysis of IgG subclass deficiency. : First reported case of IgG2,IgG4 and IgA deficiency caused by deletion of Cα1,ψCγ1,Cγ2,Cγ4 and Cεin a Mongoloid patient"J.Allergy Clin.Immunol.. 108. 602-606 (2001)

[Publications] Suzuki H., et al.: "The N-terminal region of BLM is required for the formation of dots/rod-like structure which are associated with SUMO-1"Biochem.Biophys.Res.Commun.. 286. 322-327 (2001)

[Publications] Kaneko H., et al.: "Detection of the genes induced in activated lymphocytes by modified differential display"J.Investig.Allergol.Clin.Immunol.. (in press). (2002)

[Publications] Watanabe M., et al.: "Predominant expression of 950delCAG of IL-18R alpha chain cDNA is associated with reduced IFN-gamma production and high serum IgE level in atopic patients"J.Allergy Clin.Immunol.. (in press). (2002)

金子英雄岐阜大学, 医学部・附属病院, 講師 (80293554)