2024-03-29T06:47:12Z
https://nagoya.repo.nii.ac.jp/oai
oai:nagoya.repo.nii.ac.jp:00022726
2023-01-16T04:12:14Z
336:695:696
Parallel Regulation of von Hippel-Lindau Disease by pVHL-Mediated Degradation of B-Myb and Hypoxia-Inducible Factor α
Okumura, Fumihiko
Uematsu, Keiji
Byrne, Stuart D.
Hirano, Mie
Joo-Okumura, Akiko
Nishikimi, Akihiko
Shuin, Taro
Fukui, Yoshinori
Nakatsukasa, Kunio
Kamura, Takumi
open access
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.
American Society for Microbiology
2016-06
eng
journal article
VoR
http://hdl.handle.net/2237/24879
https://nagoya.repo.nii.ac.jp/records/22726
https://doi.org/10.1128/MCB.00067-16
0270-7306
MOLECULAR AND CELLULAR BIOLOGY
36
12
1803
1817
https://nagoya.repo.nii.ac.jp/record/22726/files/Mol_Cell_Biol_2016-Okumura-1803-17.pdf
application/pdf
1.8 MB
2018-02-22