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Molecular mechanisms that integrate 'cell death and cell cycle progression.

Research Project

Project/Area Number 13043003
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionRIKEN (2004-2005)
Chiba University (2001-2003)

Principal Investigator

KOSEKI Haruhiko  RIKEN, Developmental Genetics Group, Group Director, 免疫器官形成研究グループ, グループディレクター (40225446)

Co-Investigator(Kenkyū-buntansha) KAMII Takehiko  Shinshu University, Hospital, Lecturer, 医学部附属病院, 講師 (90262708)
Project Period (FY) 2001 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥72,600,000 (Direct Cost: ¥72,600,000)
Fiscal Year 2005: ¥12,500,000 (Direct Cost: ¥12,500,000)
Fiscal Year 2004: ¥19,500,000 (Direct Cost: ¥19,500,000)
Fiscal Year 2003: ¥13,400,000 (Direct Cost: ¥13,400,000)
Fiscal Year 2002: ¥14,000,000 (Direct Cost: ¥14,000,000)
Fiscal Year 2001: ¥13,200,000 (Direct Cost: ¥13,200,000)
KeywordsPolycomb / knockout / cellular senescence / translational regulation / Pc12 / ポリコーム群 / Hox / Ink4a / 胎児性繊維芽細胞 / マウス / Ring1B / X染色体 / ヒストンH2A / ユビキチン化 / MBLR / E2F6複合体 / ホメオプロテインインターラクティングキナーゼ / プログラム細胞死 / ノックアウトマウス / クロマチン / Mel-18 / 細胞死制御 / p53
Research Abstract

We have newly identified Polycomblike 2 (Pc12) gene product as a component of Polycomb Repressive Complex-1 (PRC 1) although Pc12 had been identified as a PRC2 component previously. We have generated Pc12 deficient mice and revealed its novel role to link PRC1 and PRC2. Although PRC1 mutant MEFs (mouse embryonic fibroblasts) are shown to undergo premature senescence, Pc12-deficient MEFs cancelled senescence and subsequently transformed. This suggests Pc12 acts as a tumor suppressor. Indeed, biochemical analysis revealed that Pc12 deficiency results in stable repression of Ink4a gene through the stabilization of PRC1. Concordantly, Phc2/Pc12 doubly deficient MEFs eventually cancelled senescence, which was accompanied by genomic loss of Ink4a gene. Since stabilization of PRC1 in Pcl2 deficient MEFs was not associated with increase of transcription of mRNA encoding PRC1 components, this stabilization was expected to be mediated either by translational regulation or protein stability. To address this issue, we have first identified binding proteins for Pc12 by pull-down of TAP-tagged Pcl2 upon overexpression in 293T cells, where proteins involved in translational regulation was overrepresented such as Ribosomal proteins, RNA helicases, and RNA binding proteins. In addition, mRNA encoding PRC1 components were overrepresented within untranslated fractions of polysomes in Pc12 deficient MEFs. Together with presence of Tudor domain, which may contributes to RNA binding, Pc12 is likely involved in translational regulation of PRC1 components.

Report

(6 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (48 results)

All 2006 2005 2004 2003 2002 2001 2000 Other

All Journal Article (30 results) Publications (18 results)

  • [Journal Article] Distinct roles of Polycomb group gene products between transcriptionally repressed and active domains of Hoxb82006

    • Author(s)
      Fujimura Y
    • Journal Title

      Development 133

      Pages: 2371-2381

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Control of Developmental Regulators by Polycomb in Human Embryonic Stem Cells2006

    • Author(s)
      Lee T. I
    • Journal Title

      Cell 125

      Pages: 301-313

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Overlapping roles for homeodomain-interacting protein kinases Hipk1 and Hipk2 in the mediation of cell growth in response to morphogenetic and genotoxic signals2006

    • Author(s)
      Isono K
    • Journal Title

      Molecular and Cellular Biology 26

      Pages: 2758-2571

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Control of Developmental Regulators by Polycomb in Human Embryonic Stem Cells2006

    • Author(s)
      Lee T.I., Jenner R.G.., Boyer L.A., Guenther M.G.., Levine S.S., Kumar R.M., Chevalier B, Johnstone S.E., Cole M.F., Isono K, Koseki H, Fuchikami T, Abe K, Murray H.L.Zucker J.P., Yuan B, Bell G.W., Herbolsheimer E, Hannett N.M., Sun K, Odom D.T., Volkert T.L., Bartel D.P, Melton D.A., Gifford D.K., Jaenisch R, Young R.A.
    • Journal Title

      Cell 125(2)

      Pages: 301-13

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Overlapping roles for homeodomain-interacting protein kinases Hipkl and Hipk2 in the mediation of cell growth in response to morphogenetic and genotoxic signals.2006

    • Author(s)
      Isono, K., Nemoto, K., Li, Y., Takada, Y., Suzuki, R., Katsuki, M., Nakagawara, A., Koseki, H.
    • Journal Title

      Molecular and Cellular Biology. 26(7)

      Pages: 2758-71

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Oyerlapping roles for homeodomain-interacting protein kinases Hipk1 and Hipk2 in the mediation of cell growth in response to morphogenetic and genotoxic signals2006

    • Author(s)
      Isono K
    • Journal Title

      Molecular and Cellular Biology (印刷中)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Mammalian polyhomeotic homologues Phc2 and Phc1 act in synergy to mediate Polycomb-repression of Hox genes2005

    • Author(s)
      Isono K
    • Journal Title

      Molecular and cellular Biology 25

      Pages: 6694-6706

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Mammalian Polycomb-mediated repression of Hox genes requires the essential spliceosomal protein sf3b12005

    • Author(s)
      Isono K
    • Journal Title

      Gene Dev. 19

      Pages: 536-541

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Mammalian polyhomeotic homologues Phc2 and Phc 1 act in synergy to mediate Polycomb-repression of Hox genes.2005

    • Author(s)
      Isono K, Fujimura Y, Shinga J, Yamaki M, 0-Wang J, Takihara Y, Murahashi Y, Takada Y, Mizutani-Koseki Y, Koseki H.
    • Journal Title

      Molecular and Cellular Biology. 25(15)

      Pages: 6694-706

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Mammalian Polycomb-mediated repression of Hox genes requires the essential spliceosomal protein sf3b1.2005

    • Author(s)
      Isono K, Mizutani-Koseki Y, Komori T, Schmidt-Zachmann M.S, Koseki H.
    • Journal Title

      Gene Dev. 19(5)

      Pages: 536-41

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Mammalian Polycomb-mediated repression of Hox genes requires the essential spliceosomal protein sf3b12005

    • Author(s)
      Isono K
    • Journal Title

      Gene Dev. 19・5

      Pages: 536-541

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Topors, a p53 and topoisomerase I-binding RING finger protein, is a co-activator of p53 in growth suppression induced by DNA damage2005

    • Author(s)
      Lin L
    • Journal Title

      Oncogene 24・21

      Pages: 3385-3396

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Mammalian polyhomeotic homologues Phc2 and Phc1 act in synergy to mediate Polycomb-repression of Hox genes2005

    • Author(s)
      Isono K
    • Journal Title

      Molecular and Cellular Biology 25・15

      Pages: 6694-6706

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Topors, a p53 and topoisomerase I-binding RING finger protein, is a co-activator of p53 in growth suppression induced by DNA damage2005

    • Author(s)
      Lin L
    • Journal Title

      Oncogene. (印刷中)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Mammalian Polycomb-mediated repression of Hox genes requires the essential spliceosomal protein sf3b12005

    • Author(s)
      Isono K
    • Journal Title

      Gene Dev. (印刷中)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Polycomb-group proteins Ring 1A/B link ubiquitylation of histone H2 A to heritable gene silencing and X inactivation.2004

    • Author(s)
      Napoles M
    • Journal Title

      Dev. Cell 7

      Pages: 663-676

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Polycomb-group proteins RinglA/B link ubiquitylation of histone H2A to heritable gene silencing and X inactivation.2004

    • Author(s)
      Napoles M, Mermoud J, Wakao R, Tang Y.A, Endoh M, Appanah R, Nesterova T, Silva J, Otte A.P, Vidal M, KosekiH, Brockdorff N.
    • Journal Title

      Dev. Cell 7(5)

      Pages: 663-76

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Polycomb-group proteins Ring1A/B link ubiquitylation of histone H2A to heritable gene silencing and X inactivation2004

    • Author(s)
      Napoles M
    • Journal Title

      Dev. Cell 7・5

      Pages: 663-676

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Enhanced self-renewal of hematopoietic stem cells mediated by the polycomb gene product Bmi-12004

    • Author(s)
      Iwama A
    • Journal Title

      Immunity 21・6

      Pages: 843-851

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Requirement for Mab2112 during development of murine retina and ventral body wall2004

    • Author(s)
      Yamada R
    • Journal Title

      Dev Biol. 274・2

      Pages: 295-307

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Dilated cardiomyopathy caused by aberrant endoplasmic reticulum quality control in mutant KDEL receptor transgenic mice.2004

    • Author(s)
      Hamada H
    • Journal Title

      Mol Cell Biol. 24・18

      Pages: 8007-8017

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Hox/reporter fusions transcriptionally silenced in Polycomb mutants2003

    • Author(s)
      d Graaff W
    • Journal Title

      Proc Natl Acad Sci U S A 100

      Pages: 13362-13367

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Randomly inserted and targeted Hox/reporter fusions transcriptionally silenced in Polycomb mutants.2003

    • Author(s)
      d Graaff W, Tomotsune D, Oosterveen T, Takihara Y, Koseki H, Deschamps J.
    • Journal Title

      Pmc Natl Acad Sci U S A.1l 100(23)

      Pages: 13362-7

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Involvement of the Polycomb-group gene Ring1B in the specification of the anterior-Posterior axis in mice2002

    • Author(s)
      Suzuki M
    • Journal Title

      Development 129

      Pages: 4171-4183

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Involvement of the Polycomb-group gene Ring1B in the specification of the anterior-posterior axis in mice.2002

    • Author(s)
      Suzuki, M., Mizutani-Koseki, Y., Fujimura, Y., Miyagishima, H.Kaneko, T., Takada, Y., Akasaka, T., Tanzawa, H., Taldhara, Y., Nakano, M., Masumoto, H., Vidal, M., Isono K.Koseki, H.
    • Journal Title

      Development 129

      Pages: 4171-4183

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The role of Presenilin1 during somite segmentation.2001

    • Author(s)
      Koizumi K
    • Journal Title

      Development 128

      Pages: 1391-1402

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Mice doubly deficient for the Polycomb-Groupe genes Mel18 and Bmi1 reveal synergy and requirement for maintenance but not initiaticn of Hox gene exuression.2001

    • Author(s)
      Akasaka T
    • Journal Title

      Development 128

      Pages: 1587-1597

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The role of Presenilin1 during somite segmentation.2001

    • Author(s)
      Koizumi, K., Nakajima, M., Yuasa, S., Saga, Y., Sakai, T., Kuriyama, T., Shirasawa, T., Koseki,H.
    • Journal Title

      Development 128

      Pages: 1391-1402

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Mice doubly deficient for the Polycomb-Groupe genes Me118 and Bmil reveal synergy and requirement for maintenance but not initiation of Hox gene expression.2001

    • Author(s)
      Akasaka, T., van Lohuizen, M.van der Lugt, N., Mizutani-Koseki, Y., Kanno, M., Taniguchi, M., Vidal, M., Alkema, M., Berns, A., Koseki,H.
    • Journal Title

      Development. 128

      Pages: 1587-1597

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Distinct roles of Polycomb group gene products between transcriptionally repressed and active domains of Hoxb8.2000

    • Author(s)
      Fujimura Y, Isono K, Vidal M, Endoh M, Kajita H, Mizutani-Koseki Y, Takihara Y, van Lohuizen M, Otte A, Jenuwein T, Deschamps J, Koseki H
    • Journal Title

      Development 133(12)

      Pages: 2371-2381

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Publications] Fukuda K.: "Mesenchymal expression of Foxl1, a winged helix transcriptional factor, regulates generation and maintenance of gut associated lymphoid organs."Dev.Biol.. 255. 278-289 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamada R.: "Cell-autonomous involvement of Mab21/1 is essential for lens placode development."Development. 130. 1759-1770 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Miyagishima, H.: "Dissociation of mammalian Polycomb-group proteins, Ring1B and Rae2s/Ph1, from the chromatin correlates with configuration changes of the chromatin in mitotic and meiotic prophase."Histochem Cell Biol. 120. 111-119 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] d Graaff W: "Randomly inserted and targeted Hox/reporter fusions transcriptionally silenced in Polycomb mutants."Proc Natl Acad Sci U S A. 22. 13362-13367 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kaneko T: "The mouse YAF2 gene generates two distinct transcripts and is expressed in pre-and postimplantation embryos."Gene. 315. 183-192 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamamoto K: "The KDEL receptor modulates the endoplasmic reticulum stress response through mitogen-activated protein kinase signaling cascades."J Biol Chem.. 278. 34525-34532 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Miki, T: "Mouse model of Prinzmetal angina by disruption of the inward rectifier Kir6.1"Nature Med. 8. 466-472 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Murakami, H: "Elbow knee synostosis (Eks) : A new mutation on mouse Chromosome 14"Mammalian Genome. 13. 341-344 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamaki, M: "The mouse Edr2 (Mph2) gene has two forms of mRNA encoding 90-and 36-kDa polypeptides"Gene. 288. 103-110 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Suzuki, M: "Involvement of the Polycomb-group gene Ring1B in the specification of the anterior-posterior axis in mice"Development. 129. 4171-4183 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Akaska, T: "MBLR, a new RING finger protein resembling mammalian Polycomb gene products, is regulated by cell cycle-dependent phosphorylation"Genes Cells. 7. 835-350 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fukuda, K: "Mesenchymal expression of Foxl1, a winged helix transcriptional factor, regulates generation and maintenance of gut associated lymphoid organs"Dev. Biol.. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Akasaka T.: "Mice doubly deficient for the Polycomb-Groupe genes Mel18 and Bmi1 reveal synergy and requirement for maintenance but not initiation of Hox gene expression"Development. 128. 1587-1597 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamamoto K.: "The KDEL receptor mediates a retrieval mechanism that contributes to quality control at the endoplasmic reticulum"The EMBO Journal. 20. 3082-3091 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Isono K.: "Molecular cloning, genetic mapping, and expression of the mouse Sf3b1 (SAP155) gene for the U2 snRNP component of spliceosome"Mammalian Genome. 12. 192-198 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Koizumi K.: "The role of Presenilin 1 during somite segmentation"Development. 128. 1391-1402 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kimura M.: "Regulation of Th2 Cell Defferentiation by mel-18, a Mammaalian Polycomb Group Gene"Immunity. 15. 275-287 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ogita J.: "Expression of the Dan gene during chicken embryonic development"Mechanisms of Development. 109. 363-365 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2018-03-28  

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