2002 Fiscal Year Annual Research Report

Peutz-Jeghers症候群の原因遺伝子LKB1/STK11の機能解析

Research Project

Project/Area Number	13470033
Research Institution	The University of Tokyo
Principal Investigator	秋山徹東京大学, 分子細胞生物学研究所, 教授 (70150745)
Keywords	Peutz-Jeghers症候群 / 過誤腫性ポリポーシス / LKB1 / STK11 / LKB1AP / 好発癌性疾患 / セリン・スレオニンキナーゼ
Research Abstract	消化管の過誤腫性ポリポーシスと口唇、口囲、口腔内、指趾の特有な色素斑を合併する遺伝性の好発癌性疾患Peutz-Jeghers症候群の原因遺伝子LKB1/STK11の産物が、どのようなシグナル伝達経路で機能しているのかを明らかにすることを目的として研究を進め以下の結果を得た。1)yeast two-hybrid法およびアフィニティー精製-MS法によりLKB1/STK11結合蛋白質を検索し、LMO familyの転写共役因子がLKB1/STK11蛋白質と結合することを見出した。2)LMO familyは転写因子GATAと相互作用し、GATAによる転写を活性化するが、LKB1/STK11はGATAによる転写を活性化する。3)LKB1/STK11がCDKインヒビターp21の転写をp53と協調して活性化する。この系にはLMO family、LMOを相互作用することの知られているアダプター蛋白質Ldb1、GATA6が関与している。4)HeLa、G361細胞にLKB1/STK11を過剰発現するとG1 arrestが誘導される。この時、p21の転写が活性化する。5)さらに、LKB1/STK11によりリン酸化を受ける基質蛋白質の同定を試みたが有力な基質候補はまだ見出されていない。

Research Products
(11 results)

All Other

All Publications (11 results)

[Publications] T.Okabe: "RICS, a novel GTPase-Activating Protein for Cdc42 and Rac1, is involved in the b-catenin-N-cadherin and NMDA receptor signaling"J. Biol. Chem.. (in press).
[Publications] Y.Kawasaki: "Mutated APC and Asef are Involved in Migration of Colorectal Tumor Cells"Nature Cell Biology. 5(3). 211-215 (2003)
[Publications] T.Jimbo: "Identification of link between the Tumor Suppressor APC and the Kinesin Superfamily of Proteins"Nature Cell Biol.. 4. 323-327 (2002)
[Publications] T.Sekiya: "Overexpression of Icat Induces G2 Arrest and Cell Death in Tumor Cells Mutant for APC, β-catenin or Axin"Cancer Res.. 62. 3322-3326 (2002)
[Publications] B.C.Roy: "SPAL, a Rap-specific GTPase Activating Protein, is Present in the NMDA receptor-PSD-95 Complex in the Hippocampus"Genes Cells. 7. 607-617 (2002)
[Publications] K.Kohu: "The SH3, HOOK and Guanylate Kinase-like Domains of hDLG are Important for its Cytoplasmic Localization"Genes Cells. 7. 707-715 (2002)
[Publications] Kim M.: "Binding of the mammalian homolog of he Drosophila discs large tumor suppressor protein to the ribosome receptor"Biochem Biophys Res Commun.. 294. 1151-1154 (2002)
[Publications] T.Koyama: "Mutation and expression of the β-catenin-interacting rotein ICAT in human colorectal tumors"Jpn. J. Clin. Oncol.. 358-362 (2002)
[Publications] F.Ogawa: "Binding of the Human Homolog of the Drosophila Discs Large Tumor Suppressor Protein to the Mitochondrial Ribosomal Protein MRP-S34"Biochem. Biophys. Res. Commun.. 294. 1151-1154 (2002)
[Publications] Takemura M.: "Phosphorylation-dependent migration of retinoblastoma protein into the nucleolus triggered by binding to nucleophosmin/B23"Exp. Cell Res.. 276. 233-241 (2002)
[Publications] H.Seo: "Incorporation of DUF/FACT into chromatin enhances the accessibility of nucleosomal DNA"Biochem. Biophys. Res. Commun.. (in press). (2002)

2002 Fiscal Year Annual Research Report

Peutz-Jeghers症候群の原因遺伝子LKB1/STK11の機能解析

Principal Investigator

秋山 徹 東京大学, 分子細胞生物学研究所, 教授 (70150745)

Research Products

[Publications] T.Okabe: "RICS, a novel GTPase-Activating Protein for Cdc42 and Rac1, is involved in the b-catenin-N-cadherin and NMDA receptor signaling"J. Biol. Chem.. (in press).

[Publications] Y.Kawasaki: "Mutated APC and Asef are Involved in Migration of Colorectal Tumor Cells"Nature Cell Biology. 5(3). 211-215 (2003)

[Publications] T.Jimbo: "Identification of link between the Tumor Suppressor APC and the Kinesin Superfamily of Proteins"Nature Cell Biol.. 4. 323-327 (2002)

[Publications] T.Sekiya: "Overexpression of Icat Induces G2 Arrest and Cell Death in Tumor Cells Mutant for APC, β-catenin or Axin"Cancer Res.. 62. 3322-3326 (2002)

[Publications] B.C.Roy: "SPAL, a Rap-specific GTPase Activating Protein, is Present in the NMDA receptor-PSD-95 Complex in the Hippocampus"Genes Cells. 7. 607-617 (2002)

[Publications] K.Kohu: "The SH3, HOOK and Guanylate Kinase-like Domains of hDLG are Important for its Cytoplasmic Localization"Genes Cells. 7. 707-715 (2002)

[Publications] Kim M.: "Binding of the mammalian homolog of he Drosophila discs large tumor suppressor protein to the ribosome receptor"Biochem Biophys Res Commun.. 294. 1151-1154 (2002)

[Publications] T.Koyama: "Mutation and expression of the β-catenin-interacting rotein ICAT in human colorectal tumors"Jpn. J. Clin. Oncol.. 358-362 (2002)

[Publications] F.Ogawa: "Binding of the Human Homolog of the Drosophila Discs Large Tumor Suppressor Protein to the Mitochondrial Ribosomal Protein MRP-S34"Biochem. Biophys. Res. Commun.. 294. 1151-1154 (2002)

[Publications] Takemura M.: "Phosphorylation-dependent migration of retinoblastoma protein into the nucleolus triggered by binding to nucleophosmin/B23"Exp. Cell Res.. 276. 233-241 (2002)

[Publications] H.Seo: "Incorporation of DUF/FACT into chromatin enhances the accessibility of nucleosomal DNA"Biochem. Biophys. Res. Commun.. (in press). (2002)

秋山徹東京大学, 分子細胞生物学研究所, 教授 (70150745)