2005 Fiscal Year Final Research Report Summary
Molecular mechanisms that integrate 'cell death and cell cycle progression.
| Project/Area Number |
13043003
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | RIKEN (2004-2005)
Chiba University (2001-2003) |
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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)
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| Co-Investigator(Kenkyū-buntansha) |
KAMII Takehiko Shinshu University, Hospital, Lecturer, 医学部附属病院, 講師 (90262708)
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| Project Period (FY) |
2001 – 2005
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| Keywords | Polycomb / knockout / cellular senescence / translational regulation / Pc12 |
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| 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.
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[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.
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Journal Title
Cell 125(2)
Pages: 301-13
Description
「研究成果報告書概要(欧文)」より
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[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.
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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
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[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.
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Journal Title
Dev. Cell 7(5)
Pages: 663-76
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Development 129
Pages: 4171-4183
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Development 128
Pages: 1391-1402
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Development. 128
Pages: 1587-1597
Description
「研究成果報告書概要(欧文)」より
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[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
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Journal Title
Development 133(12)
Pages: 2371-2381
Description
「研究成果報告書概要(欧文)」より
