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Parallel Regulation of von Hippel-Lindau Disease by pVHL-Mediated Degradation of B-Myb and Hypoxia-Inducible Factor α
http://hdl.handle.net/2237/24879
http://hdl.handle.net/2237/24879c6ab3ece-e42b-459c-8f46-af7f52244755
名前 / ファイル | ライセンス | アクション |
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Mol_Cell_Biol_2016-Okumura-1803-17.pdf (1.8 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2016-09-27 | |||||
タイトル | ||||||
タイトル | Parallel Regulation of von Hippel-Lindau Disease by pVHL-Mediated Degradation of B-Myb and Hypoxia-Inducible Factor α | |||||
言語 | en | |||||
著者 |
Okumura, Fumihiko
× Okumura, Fumihiko× Uematsu, Keiji× Byrne, Stuart D.× Hirano, Mie× Joo-Okumura, Akiko× Nishikimi, Akihiko× Shuin, Taro× Fukui, Yoshinori× Nakatsukasa, Kunio× Kamura, Takumi |
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アクセス権 | ||||||
アクセス権 | open access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | pVHL, the protein product of the von Hippel-Lindau (VHL) tumor suppressor gene, is a ubiquitin ligase that targets hypoxia-inducible factor α (HIF-α) for proteasomal degradation. Although HIF-α activation is necessary for VHL disease pathogenesis, constitutive activation of HIF-α alone did not induce renal clear cell carcinomas and pheochromocytomas in mice, suggesting the involvement of an HIF-α-independent pathway in VHL pathogenesis. Here, we show that the transcription factor B-Myb is a pVHL substrate that is degraded via the ubiquitin-proteasome pathway and that vascular endothelial growth factor (VEGF)- and/or platelet-derived growth factor (PDGF)-dependent tyrosine 15 phosphorylation of B-Myb prevents its degradation. Mice injected with B-Myb knockdown 786-O cells developed dramatically larger tumors than those bearing control cell tumors. Microarray screening of B-Myb-regulated genes showed that the expression of HIF-α-dependent genes was not affected by B-Myb knockdown, indicating that B-Myb prevents HIF-α-dependent tumorigenesis through an HIF-α-independent pathway. These data indicate that the regulation of B-Myb by pVHL plays a critical role in VHL disease. | |||||
言語 | en | |||||
出版者 | ||||||
出版者 | American Society for Microbiology | |||||
言語 | en | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
出版タイプ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
DOI | ||||||
関連タイプ | isVersionOf | |||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.1128/MCB.00067-16 | |||||
ISSN | ||||||
収録物識別子タイプ | PISSN | |||||
収録物識別子 | 0270-7306 | |||||
書誌情報 |
en : MOLECULAR AND CELLULAR BIOLOGY 巻 36, 号 12, p. 1803-1817, 発行日 2016-06 |
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値 | publisher | |||||
URI | ||||||
識別子 | http://doi.org/10.1128/MCB.00067-16 | |||||
識別子タイプ | DOI | |||||
URI | ||||||
識別子 | http://hdl.handle.net/2237/24879 | |||||
識別子タイプ | HDL |
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Okumura, Fumihiko, Uematsu, Keiji, Byrne, Stuart D., Hirano, Mie, Joo-Okumura, Akiko, Nishikimi, Akihiko, Shuin, Taro, Fukui, Yoshinori, Nakatsukasa, Kunio, Kamura, Takumi, 2016, Parallel Regulation of von Hippel-Lindau Disease by pVHL-Mediated Degradation of B-Myb and Hypoxia-Inducible Factor α: American Society for Microbiology, 1803–1817 p.
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