Functiona analysis of tumor suppressor gene product pVHL
| Project/Area Number |
25291023
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Functional biochemistry
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| Research Institution | Nagoya University |
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Principal Investigator |
Kamura Takumi 名古屋大学, 理学(系)研究科(研究院), 教授 (40333455)
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| Co-Investigator(Kenkyū-buntansha) |
Okumura Fumihiko 名古屋大学, 大学院理学研究科, 助教 (00507212)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2015: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
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| Keywords | タンパク質分解 / ガン / 癌 / 蛋白質分解 |
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| Outline of Final Research Achievements |
pVHL is a ubiquitin ligase that targets hypoxia-inducible factor-alpha (HIF-alpha) for proteasomal degradation. Although HIF-alpha activation is necessary for VHL disease pathogenesis, constitutive activation of HIF-alpha alone did not induce renal clear cell carcinomas and pheochromocytomas in mice, suggesting the involvement of HIF-alpha-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. 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-alpha-dependent genes was not affected by B-Myb knockdown, indicating that B-Myb prevents HIF-alpha-dependent tumorigenesis through a HIF-alpha-independent pathway. These data indicate that the regulation of B-Myb by pVHL plays a critical role in VHL disease.
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Report
(4 results)
Research Products
(22 results)
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[Journal Article] Parallel regulation of VHL disease by pVHL-mediated degradation of B-Myb and HIF-α2016
Author(s)
Okumura, F., Uematsu, K., Byrne, S.D., Hirano, M., Okumura, A. J., Nishikimi, A., Shuin, T., Fukui, Y., Nakatsukasa, K. & Kamura, T.
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Journal Title
Mol. Cell. Biol.
Volume: in press
Related Report
Peer Reviewed / Acknowledgement Compliant
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