1996 Fiscal Year Annual Research Report

細胞分裂周期における染色体の伝達分配機構の研究

Research Project

Project/Area Number	05102004
Research Institution	KYOTO UNIVERSITY
Principal Investigator	柳田充弘京都大学, 大学院・理学研究科, 教授 (80025428)
Co-Investigator(Kenkyū-buntansha)	中世古幸信京都大学, 大学院・理学研究科, 助手 (30231468)
Keywords	細胞周期 / 染色体 / サイクリン / タンパク質分解 / ストレス / 環状AMP / 染色体分配
Research Abstract	染色体分配に必須なタンパク質として研究をしてきたCut2はそのアミノ末端に二つの破壊シグナルを有し,細胞周期M期後期にユビキチン依存的に分解することを見いだし,これがサイクリンの分解を行っているAPC/サイクロソーム複合体の有するユビキチンリガーゼ活性に依存することを明らかにした。cut2の分解が起こらないと染色体分配が起こらない。もしもN端を欠失したCut2を細胞内に導入すると、分解されず、染色体分配も起こらない。さらにCut2分解とサイクリ分解は類似しており、Cut2のN端の部分をサイクリンのN端と置き換えても機能が有する。Cut2はCut1分子と結合し、M期の中期の時点までは染色分体の分離に働き、後期では壊れて分配の振興を妨げないという働きをする。これらの研究はNature、EMBOJに公表された。培地依存的にM期中期で停止するcut4遺伝子産物がAPC/サイクロソーム複合体のサブユニットであることが判明した。しかもこのタンパク質は酵母からヒトまで高い相同性で保存されていた。cut4変異は培地中の重金属、アミノ酸アナログ、環状AMPに感受性であり、その時M期中期で停止する興味深い表現型は示した。一方変異体細胞中に環状AMP依存性ホスホジエステラーゼ(PDE)遺伝子やPKAキナーゼの制御サブユニット遺伝子(RAK)を導入すると、変異は抑制された。さらに、cut4変異細胞中ではAPC/サイクロソームは壊れていたが、抑制された細胞ではAPC/サイクロソーム複合体は回復していた。このことから、cut4タンパク質はストレスやPKAバスウエーに制御され、それ結果M期におけるタンパク分解も同様に制御されていると推測された。この研究はNatureに公表された。

Research Products
(16 results)

All Other

All Publications (16 results)

[Publications] Yukiko M.Yamashita: "20S cyclosome complex formation and proteolytic activity inhibited by the cAMP/PKA pathway." Nature. 384. 276-279 (1996)
[Publications] Hironori Funabiki: "Fission yeast Cut1 and Cut2 are essential for sister chromatid separation concentrate along the methaphase spindle and form large complexes" The EMBO Journal. 15. 6617-6628 (1996)
[Publications] Hironari Funabiki: "Cut2 proteolysis required for sister-chromatid separation in fission yeast" Nature. 381. 438-441 (1996)
[Publications] Kojiro Ishii: "Requirement for PP1I phosphatase and 20S cyclosomel APC for the on set of anaphas" The EMBO Journal. 15. 6629-6640 (1996)
[Publications] Kazahisa Kinoshita: "The regulatory subunits of tission yeast protein phosphatase ZA(PP2A) affect cell morphogenesis,cell wall synthesis and cytokinesis" Genes to Cells. 1. 29-45 (1996)
[Publications] Yukinobu Nakaseko: "Dissection of fission yeast micro tubule associating protein pa3^<Dis1> regions implicated in regulated localization and micro tubule interaction" Genes to Cells. 1. 633-644 (1996)
[Publications] Saka,Y.,Fantes,P.,Sutani,T.,McInerny,C.,Creanor,J.and Yanagida,M.: "Fission yeast cut5 links nuclear chromatin and M phase regulator in the replication checkpont control" EMBO J.13. 5319-5329 (1994)
[Publications] Saka,Y.,Fantes,P.and Yanagida,M.: "Coupling of DNA replication and mitosis by fission yeast rad 41 cut 5." J.Cell Sci.supplement. 18(in press). (1994)
[Publications] Somejima,I.and Yanagida,M.: "Identification of cut8^+ and cek1^+,a novel protein kinase gene,which complement a fission yeast mutation that blocks anophase." Mol.Cell.Biol.14. 6361-6371 (1994)
[Publications] Takahashi,K.,Yamada,H.and Yanagida,M.: "Fission yeast minichromosome loss mutants mic cause lethal anveploidy and replication abnormality." Mol.Biol.Cell. 5. 1145-1158 (1994)
[Publications] Yamano,H.,Ishii,K.and Yanagida,M.: "Phosphorylation of dis2 protein phosphatase at the C-terminal cdc2 consensus and its potential role in cell cycle regulation." EMBO J.13. 5310-5318 (1994)
[Publications] Yoshida,T.,Toda,T.and Yanagida,M.: "A calcineurin-like gene ppb1^+ in fission yeast : mutant defects in cytokinesis,cell polarity,mating and spindle pole body positioning." J.Cell Sci.107. 1725-1735 (1994)
[Publications] Chikashige,Y.,Ding,D.-Q.,Funabik,H.,Haraguchi,T.,Mashiko,S.,Yanagida,M.and Hiraoka,Y.: "Telomere-led premeiotic chromosome movement in fission yeast" Science. 264. 270-273 (1994)
[Publications] Kobori,H.,Toda,T.,Yaguchi,H.,Toya,M.,Yanagida,M.and Osumi,M.: "Fission yeast protein kinase C gene homologues are required for protoplast regeneration : a functional link between cell wall formation and cell shape." J.Cell Sci. 107. 1131-1136 (1994)
[Publications] Saka,Y.,Sutani,T.,Yamashita,Y.,Saitoh,S.,Takeuchi,M.,Nakaseko,Y.and Yanagida,M.: "Fission yeast cut3 and cut14,members of the ubiquitous protein family,are required for chromesome condensation and segregation in mitosis." EMBO J.13. 4938-4952 (1994)
[Publications] Samejima,I.and Yanmagida,M.: "Bypassing anaphase in fission yeast cut9 mutation : requirement of cut 9^+ to initiate anaphase." J.Cell Biol.127. 1655-1670 (1994)

1996 Fiscal Year Annual Research Report

細胞分裂周期における染色体の伝達分配機構の研究

Principal Investigator

柳田 充弘 京都大学, 大学院・理学研究科, 教授 (80025428)

Research Products

[Publications] Yukiko M.Yamashita: "20S cyclosome complex formation and proteolytic activity inhibited by the cAMP/PKA pathway." Nature. 384. 276-279 (1996)

[Publications] Hironori Funabiki: "Fission yeast Cut1 and Cut2 are essential for sister chromatid separation concentrate along the methaphase spindle and form large complexes" The EMBO Journal. 15. 6617-6628 (1996)

[Publications] Hironari Funabiki: "Cut2 proteolysis required for sister-chromatid separation in fission yeast" Nature. 381. 438-441 (1996)

[Publications] Kojiro Ishii: "Requirement for PP1I phosphatase and 20S cyclosomel APC for the on set of anaphas" The EMBO Journal. 15. 6629-6640 (1996)

[Publications] Kazahisa Kinoshita: "The regulatory subunits of tission yeast protein phosphatase ZA(PP2A) affect cell morphogenesis,cell wall synthesis and cytokinesis" Genes to Cells. 1. 29-45 (1996)

[Publications] Yukinobu Nakaseko: "Dissection of fission yeast micro tubule associating protein pa3^<Dis1> regions implicated in regulated localization and micro tubule interaction" Genes to Cells. 1. 633-644 (1996)

[Publications] Saka,Y.,Fantes,P.,Sutani,T.,McInerny,C.,Creanor,J.and Yanagida,M.: "Fission yeast cut5 links nuclear chromatin and M phase regulator in the replication checkpont control" EMBO J.13. 5319-5329 (1994)

[Publications] Saka,Y.,Fantes,P.and Yanagida,M.: "Coupling of DNA replication and mitosis by fission yeast rad 41 cut 5." J.Cell Sci.supplement. 18(in press). (1994)

[Publications] Somejima,I.and Yanagida,M.: "Identification of cut8^+ and cek1^+,a novel protein kinase gene,which complement a fission yeast mutation that blocks anophase." Mol.Cell.Biol.14. 6361-6371 (1994)

[Publications] Takahashi,K.,Yamada,H.and Yanagida,M.: "Fission yeast minichromosome loss mutants mic cause lethal anveploidy and replication abnormality." Mol.Biol.Cell. 5. 1145-1158 (1994)

[Publications] Yamano,H.,Ishii,K.and Yanagida,M.: "Phosphorylation of dis2 protein phosphatase at the C-terminal cdc2 consensus and its potential role in cell cycle regulation." EMBO J.13. 5310-5318 (1994)

[Publications] Yoshida,T.,Toda,T.and Yanagida,M.: "A calcineurin-like gene ppb1^+ in fission yeast : mutant defects in cytokinesis,cell polarity,mating and spindle pole body positioning." J.Cell Sci.107. 1725-1735 (1994)

[Publications] Chikashige,Y.,Ding,D.-Q.,Funabik,H.,Haraguchi,T.,Mashiko,S.,Yanagida,M.and Hiraoka,Y.: "Telomere-led premeiotic chromosome movement in fission yeast" Science. 264. 270-273 (1994)

[Publications] Kobori,H.,Toda,T.,Yaguchi,H.,Toya,M.,Yanagida,M.and Osumi,M.: "Fission yeast protein kinase C gene homologues are required for protoplast regeneration : a functional link between cell wall formation and cell shape." J.Cell Sci. 107. 1131-1136 (1994)

[Publications] Saka,Y.,Sutani,T.,Yamashita,Y.,Saitoh,S.,Takeuchi,M.,Nakaseko,Y.and Yanagida,M.: "Fission yeast cut3 and cut14,members of the ubiquitous protein family,are required for chromesome condensation and segregation in mitosis." EMBO J.13. 4938-4952 (1994)

[Publications] Samejima,I.and Yanmagida,M.: "Bypassing anaphase in fission yeast cut9 mutation : requirement of cut 9^+ to initiate anaphase." J.Cell Biol.127. 1655-1670 (1994)

柳田充弘京都大学, 大学院・理学研究科, 教授 (80025428)