2010 Fiscal Year Final Research Report
The role of Anaphase-Promoting Co mplex(APC)Activator Cdh1 on cell motility
| Project/Area Number |
20590315
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Keio University |
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Principal Investigator |
KUNINAKA Shinji Keio University, 医学部, 助教 (10404336)
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| Project Period (FY) |
2008 – 2010
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| Keywords | Cdh1 / APC / Rho / p190 |
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| Research Abstract |
Cdh1 is an activator of the anaphase-promoting complex/cyclosome and contributes to mitotic exit and G1 maintenance by targeting cell-cycle proteins for degradation. Here, we found a novel function for Cdh1 as a regulator of Rho. The GTP-bound active Rho protein was apparently decreased in the Cdh1-depleted cells. Cdh1 formed a physical complex with the p190 protein, a major GAP for Rho, and stimulated the efficient ubiquitination of p190, both in in vitro and in vivo. The motility of Cdh1-depleted cells was impaired ; however, co-depletion of p190 rescued the migration activity of these cells. Moreover, homozygous Cdh1 gene-trapped mouse embryos exhibited similar phenotypes to those observed for Rho-associated kinase I and II knockout mice, suggesting the in vivo significance of Cdh1/p190/Rho axis.
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Research Products
(12 results)
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[Journal Article] Establishment of a choriocarcinoma model from immortalized normal extravillous trophoblast cells transduced with HRASV12.2011
Author(s)
Kobayashi Y, Shimizu T, Naoe H, Ueki A, Ishizawa J, Chiyoda T, Onishi N, Sugihara E, Nagano O, Banno K, Kuninaka S, Aoki D, Saya H
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Journal Title
Peer Reviewed
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[Journal Article] The cell cycle regulator Cdh1 controls the pool sizes of hematopoietic stem cells and mature lineage progenitors by protecting from genotoxic stress.2011
Author(s)
Ishizawa J, Kuninaka S, Sugihara E, Naoe H, Kobayashi Y, Chiyoda T, Ueki A, Araki K, Yamamura KI, Matsuzaki Y, Nakajima H, Ikeda Y, Okamoto S, Saya H
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Journal Title
Cancer Sci. 102
Pages: 1349-7006
Peer Reviewed
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[Journal Article] c-MYC overexpression with loss of Ink4a/Arf transforms bone marrow stromal cells into osteosarcoma accompanied by loss of adipogenesis.2010
Author(s)
Shimizu T, Ishikawa T, Sugihara E, Kuninaka S, Miyamoto T, Mabuchi Y, Matsuzaki Y, Tsunoda T, Miya F, Morioka H, Nakayama R, Kobayashi E, Toyama Y, Kawai A, Ichikawa H, Hasegawa T, Okada S, Ito T, Ikeda Y, Suda T, Saya H
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Journal Title
Oncogene 29
Pages: 5687-99
Peer Reviewed
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[Journal Article] The anaphase-promoting complex/cyclosome activator Cdh1 modulates Rho GTPase by targeting p190 RhoGAP for degradation.2010
Author(s)
Naoe H, Araki K, Nagano O, Kobayashi Y, Ishizawa J, Chiyoda T, Shimizu T, Yamamura K, Sasaki Y, Saya H, Kuninaka S
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Journal Title
Mol Cell Biol 30
Pages: 3994-4005
Peer Reviewed
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