2006 Fiscal Year Final Research Report Summary
Molecular Mechanism for Nuclear Receptor Degradation
| Project/Area Number |
17390014
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | University of Tsukuba |
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Principal Investigator |
YANAGISAWA Jun University of Tsukuba, Graduate School of Life and Environmental Sciences, professor, 大学院生命環境科学研究科, 教授 (50301114)
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| Project Period (FY) |
2005 – 2006
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| Keywords | genome / protein / gene regulation / proteome / transcription |
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| Research Abstract |
Estrogen receptor alpha (ERα) is a valuable prognostic factor in early-stage breast cancer, however, ERα-negative cancers typically exhibit higher histological grades than ERα-positive cancers during the progressive stages. In contrast, TGF-β acts as a tumor suppressor early in tumor development, but promotes invasion and metastasis at later stages. We found that exogenous expression of ERα in ERα-negative breast cancer cells abrogated TGF-β-mediated signaling pathways, reducing the invasive and metastatic potential of these cells. ERα formed a protein complex with Smad, a signal transducer in the TGF-β pathway, and Smurfs, ubiquitin ligases, to induce their ubiquitination and subsequent degradation. In human breast tumor tissues, an anticorrelation between ERα and Smad protein levels was observed. These findings suggest that ERα, opposes the effects of TGF-13 on cancer progression via a novel non-genomic mechanism. Several other nuclear receptors (NRs) tested also possessed the ability to induce Smad degradation. These observations provide new insight into non-genomic functions of NRs and the mechanisms underlying NR-mediated suppression of tumor invasion.
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[Journal Article] Turning Off Estrogen Receptor β-Mediated Transcription Requires Estrogen-Dependent Receptor Proteolysis.2006
Author(s)
Tateishi Y, Sonoo R, Sekiya Y, Sunahara N, Kawano M, Wayama M, Hirota R, Kawabe Y, Murayama A, Kato S, Kimura K, Yanagisawa J
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Journal Title
Molecular and Cellular Biology 26.21
Pages: 7966-7976
Description
「研究成果報告書概要(和文)」より
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[Journal Article] A specific CpG site demethylation in the human interleukin 2 gene promoter is an epigenetic memory.2006
Author(s)
Murayama A, Sakura K, Nakama M, Yasuzawa-Tanaka K, Fujita E, Tateishi Y, Wang Y, Ushijima T, Shibuya K, Kawabe Y, Yanagisawa J
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Journal Title
EMBO J. 25
Pages: 1081-1092
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Turning Off Estrogen Receptor 13-Mediated Transcription Requires Estrogen-Dependent Receptor Proteolysis.2006
Author(s)
Tateishi Y, Sonoo R, Sekiya Y, Sunahara N, Kawano M, Wayama M, Hirota R, Kawabe Y, Murayama A, Kato S, Kimura K, Yanagisawa J.
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Journal Title
Molecular and Cellular Biology 26.21
Pages: 7966-7976
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] A specific CpG site demethylation in the human interleukin 2 gene promoter is an epigenetic memory.2006
Author(s)
Murayama A, Sakura K, Nakama M, Yasuzawa-Tanaka K, Fujita E, Tateishi Y, Wang Y, Ushijima T, Shibuya K, Kawabe Y, Yanagisawa J.
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Journal Title
EMBO J 25
Pages: 1081-1092
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Repressive domain of unliganded human estrogen receptor alpha associates with Hsc70.2005
Author(s)
Ogawa S, Oishi H, Mezaki Y, Kouzu-Fujita M, Matsuyama R, Nakagomi M, Mori E, Murayama E, Nagasawa H, Kitagawa H, Yanagisawa J, Yano T, Kato S
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Journal Title
Genes Cells. 10・12
Pages: 1095-1102
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Repressive domain of unliganded human estrogen receptor alpha associates with Hsc70.2005
Author(s)
Ogawa S, Oishi H, Mezaki Y, Kouzu-Fujita M, Matsuyama R, Nakagomi M, Mori E, Murayama E, Nagasawa H, Kitagawa H, Yanagisawa J, Yano T, Kato S.
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Journal Title
Genes Cells. Dec 10(12)
Pages: 1095-1102
Description
「研究成果報告書概要(欧文)」より
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