2002 Fiscal Year Annual Research Report

細胞周期の開始制御

Research Project

Project/Area Number	13043005
Research Institution	The University of Tokyo
Principal Investigator	岡山博人東京大学, 大学院・医学系研究科, 教授 (40111950)
Co-Investigator(Kenkyū-buntansha)	石見幸男三菱化学生命科学研究所, 分子生命工学部, 主任研究員白髭克彦理化学研究所, 横浜研究所, 研究員大矢禎一東京大学, 大学院・新領域創成科学研究科, 教授 (20183767)
Keywords	細胞周期 / G1 / S / Cdc6 / Cdk6 / D3
Research Abstract	細胞周期のG1期は、細胞の増殖、分化、静止へ決定がなされる極めて重要な時期である。今年度も引き続き、足場非依存性S期開始機構と、発癌感受性と細胞周期開始因子との関係を検討し、下記の点を明らかにした。 1.複製開始点の活性化に必須なCdc6タンパクの発現に足場シグナルか癌化シグナルが必要である。 2.足場消失の際のCdc6の発現抑制は、転写レベルとタンパクレベルで行われている。 3.足場消失の際のCdc6タンパクの分解には、カルパイン様分解酵素が働いていて、この制御は、予想外の機構で行われているようである。 4.細胞の生存と増殖にかかわるPI3キナーゼ系が、足場存在下でのCdc6タンパクの発現に必要である。 5.細胞周期開始サイクリン依存性タンパクキナーゼのうちCdk6とサイクリンD3との複合体は、増殖抑制下の細胞の増殖能を制御できるとともに、細胞の発癌感受性を著しく上昇させる。BALBc3T3,C3H10T1/2細胞を用いた実験では、UVあるいは化学発癌剤に対する感受性が100万倍程度上昇した。一方、細胞分化の制御に係わる新規因子を同定した。これまでの一連の研究で見出した分裂酵母の分化開始制御因子のうちRcd1と名づけた因子は、窒素源枯渇による分化開始に必須である。この因子のホモログが、他の真核生物にもあり、アミノ酸配列が70%以上保存されている。このヒトホモログの機能を解明した。発生分化にかかわるレチノイン酸受容体とATF2を繋ぐ転写補助因子として働き、レチノイン酸による発生分化に深くかかわっている。

Research Products

(18 results)

All Other

All Publications (18 results)

[Publications] Tanaka, H. et al.: "The fission Yeast pfh1^+ gene encodes an essential 5' to 3' DNA helicase required for the completion of S-phase"Nucleic Acids Research. 30・22. 4728-4739 (2002)
[Publications] Hiroi, N.et al.: "Mammalian Rcd1 is a novel transcriptional cofactor that mediates retinoic acid-induced cell differentiation"The EMBO Journal. 21・19. 5235-5244 (2002)
[Publications] Jinno, S.et al.: "Cdc6 required anchorage for its expression"Oncogene. 21. 1777-1784 (2002)
[Publications] Chen, Q.et al.: "Overexpression of Cdk6-cyclin D3 highly sensitizes cells to physical and chemical transformation"Oncogene. 22. 992-1001 (2003)
[Publications] Ishimi, Y.et al.: "Enhanced expression of Mcm proteins in cancer cells derived from uterine cervix"Eur.J.Biochem.. (in press).
[Publications] You Z.et al.: "Roles of Mcm7 and Mcm4 subunits in the DNA helicase activity of the mouse Mcm4/6/7 complex"J.Biol.Chem.. 277. 42471-42479 (2002)
[Publications] Fujita M.et al.: "Nuclear organizatio of DNA replication initiation proteins in mammalian cells"J.Biol.Chem.. 277. 10354-10361 (2002)
[Publications] Yabuta, N.et al.: "Mamalian Mcm2/4/6/7 complex forms a toroidal structure"Genes Cells. (in press).
[Publications] Ishimi, Y.: "Regulation of eukaryotic DNA replication and the role of Mcm helicase"Recent Res.Devel.Mol.Cell.Biol.. 3. 47-57 (2002)
[Publications] 石見幸男: "ゲノムの複製の制御"生化学. 74. 1360-1363 (2002)
[Publications] Sekiya, -K.M.et al.: "Dissection of Upstream Regulatory Components of the Rho1p Effector, 1,3-β-Glucan Synthase, in Saccharomyces cerevisiae"Genetics. 162. 663-761 (2002)
[Publications] Utsugi, T.et al.: "Movement of yeast 1,3-β-glucan synthase on the surface of the plasma membrane"Gene to Cells. 7. 1-9 (2002)
[Publications] Mizutani, R., et al.: "Protein-splicing reaction via a thiazolidine intermediate : crystal structure of the VMA1-derived endonuclease bearing the N-and C-terminal propeptides"J.Mol.Biol.. 316. 919-929 (2002)
[Publications] Dijkgraaf, G.J.P.et al.: "Involvement of Saccharomyces cerevisiae Fks1p β-1, 6-glucan biosynthesis"Yeast. 19. 671-690 (2002)
[Publications] Nogami, S.et al.: "Karyopherin-mediated Nuclear Import of the Homing Endonuclease, VDE, Is Required for Self-propagation of the Coding Region"Mol.Cell Biol.. 23. 1726-1736 (2002)
[Publications] Okuda Y.et al.: "Occurrence, horizontal transfer and degeneration of VDE intein family in saccharomycete yeasts"Yeast. (in press). (2003)
[Publications] Abe M.et al.: "Lack of GTP-bound Rho1p in Secretory Vesicles of Saccharomyces cerevisiae"J.Cell Biol.. (in press). (2003)
[Publications] Ohtani, Sano, F.et al.: "Development of image processing program for yeast cell morphology"J.Bioinfo Comp.Biol.. (in press). (2003)

2002 Fiscal Year Annual Research Report

細胞周期の開始制御

Principal Investigator

岡山 博人 東京大学, 大学院・医学系研究科, 教授 (40111950)

Research Products

[Publications] Tanaka, H. et al.: "The fission Yeast pfh1^+ gene encodes an essential 5' to 3' DNA helicase required for the completion of S-phase"Nucleic Acids Research. 30・22. 4728-4739 (2002)

[Publications] Hiroi, N.et al.: "Mammalian Rcd1 is a novel transcriptional cofactor that mediates retinoic acid-induced cell differentiation"The EMBO Journal. 21・19. 5235-5244 (2002)

[Publications] Jinno, S.et al.: "Cdc6 required anchorage for its expression"Oncogene. 21. 1777-1784 (2002)

[Publications] Chen, Q.et al.: "Overexpression of Cdk6-cyclin D3 highly sensitizes cells to physical and chemical transformation"Oncogene. 22. 992-1001 (2003)

[Publications] Ishimi, Y.et al.: "Enhanced expression of Mcm proteins in cancer cells derived from uterine cervix"Eur.J.Biochem.. (in press).

[Publications] You Z.et al.: "Roles of Mcm7 and Mcm4 subunits in the DNA helicase activity of the mouse Mcm4/6/7 complex"J.Biol.Chem.. 277. 42471-42479 (2002)

[Publications] Fujita M.et al.: "Nuclear organizatio of DNA replication initiation proteins in mammalian cells"J.Biol.Chem.. 277. 10354-10361 (2002)

[Publications] Yabuta, N.et al.: "Mamalian Mcm2/4/6/7 complex forms a toroidal structure"Genes Cells. (in press).

[Publications] Ishimi, Y.: "Regulation of eukaryotic DNA replication and the role of Mcm helicase"Recent Res.Devel.Mol.Cell.Biol.. 3. 47-57 (2002)

[Publications] 石見幸男: "ゲノムの複製の制御"生化学. 74. 1360-1363 (2002)

[Publications] Sekiya, -K.M.et al.: "Dissection of Upstream Regulatory Components of the Rho1p Effector, 1,3-β-Glucan Synthase, in Saccharomyces cerevisiae"Genetics. 162. 663-761 (2002)

[Publications] Utsugi, T.et al.: "Movement of yeast 1,3-β-glucan synthase on the surface of the plasma membrane"Gene to Cells. 7. 1-9 (2002)

[Publications] Mizutani, R., et al.: "Protein-splicing reaction via a thiazolidine intermediate : crystal structure of the VMA1-derived endonuclease bearing the N-and C-terminal propeptides"J.Mol.Biol.. 316. 919-929 (2002)

[Publications] Dijkgraaf, G.J.P.et al.: "Involvement of Saccharomyces cerevisiae Fks1p β-1, 6-glucan biosynthesis"Yeast. 19. 671-690 (2002)

[Publications] Nogami, S.et al.: "Karyopherin-mediated Nuclear Import of the Homing Endonuclease, VDE, Is Required for Self-propagation of the Coding Region"Mol.Cell Biol.. 23. 1726-1736 (2002)

[Publications] Okuda Y.et al.: "Occurrence, horizontal transfer and degeneration of VDE intein family in saccharomycete yeasts"Yeast. (in press). (2003)

[Publications] Abe M.et al.: "Lack of GTP-bound Rho1p in Secretory Vesicles of Saccharomyces cerevisiae"J.Cell Biol.. (in press). (2003)

[Publications] Ohtani, Sano, F.et al.: "Development of image processing program for yeast cell morphology"J.Bioinfo Comp.Biol.. (in press). (2003)

岡山博人東京大学, 大学院・医学系研究科, 教授 (40111950)