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VHL promotes E2 box-dependent E-cadherin transcription by HIF-mediated regulation of SIP1 and snail
dc.contributor.author | Evans, Andrew J | |
dc.contributor.author | Russell, Ryan C | |
dc.contributor.author | Roche, Olga | |
dc.contributor.author | Burry, T Nadine | |
dc.contributor.author | Fish, Jason E | |
dc.contributor.author | Chow, Vinca W K | |
dc.contributor.author | Kim, William Y | |
dc.contributor.author | Saravanan, Arthy | |
dc.contributor.author | Maynard, Mindy A | |
dc.contributor.author | Gervais, Michelle L | |
dc.contributor.author | Sufan, Roxana I | |
dc.contributor.author | Roberts, Andrew M | |
dc.contributor.author | Wilson, Leigh A | |
dc.contributor.author | Betten, Mark | |
dc.contributor.author | Vandewalle, Cindy | |
dc.contributor.author | Berx, Geert | |
dc.contributor.author | Marsden, Philip A | |
dc.contributor.author | Irwin, Meredith S | |
dc.contributor.author | Teh, Bin T | |
dc.contributor.author | Jewett, Michael A S | |
dc.contributor.author | Ohh, Michael | |
dc.date.accessioned | 2024-02-02T12:18:08Z | |
dc.date.available | 2024-02-02T12:18:08Z | |
dc.date.issued | 2007 | |
dc.identifier.citation | Evans, A. J., Russell, R. C., Roche, O., Burry, T. N., Fish, J. E., Chow, V. W. K., Kim, W. Y., Saravanan, A., Maynard, M. A., Gervais, M. L., Sufan, R. I., Roberts, A. M., Wilson, L. A., Betten, M., Vandewalle, C., Berx, G., Marsden, P. A., Irwin, M. S., Teh, B. T., … Ohh, M. (2007). VHL Promotes E2 Box-Dependent E-Cadherin Transcription by HIF-Mediated Regulation of SIP1 and Snail. Molecular and Cellular Biology, 27(1), 157-169. https://doi.org/10.1128/MCB.00892-06 | es |
dc.identifier.issn | 0270-7306 | |
dc.identifier.uri | http://hdl.handle.net/20.500.12020/1147 | |
dc.description.abstract | The product of the von Hippel-Lindau gene (VHL) acts as the substrate-recognition component of an E3 ubiquitin ligase complex that ubiquitylates the catalytic alpha subunit of hypoxia-inducible factor (HIF) for oxygen-dependent destruction. Although emerging evidence supports the notion that deregulated accumulation of HIF upon the loss of VHL is crucial for the development of clear-cell renal cell carcinoma (CC-RCC), the molecular events downstream of HIF governing renal oncogenesis remain unclear. Here, we show that the expression of a homophilic adhesion molecule, E-cadherin, a major constituent of epithelial cell junctions whose loss is associated with the progression of epithelial cancers, is significantly down-regulated in primary CC-RCC and CC-RCC cell lines devoid of VHL. Reintroduction of wild-type VHL in CC-RCC (VHL(-/-)) cells markedly reduced the expression of E2 box-dependent E-cadherin-specific transcriptional repressors Snail and SIP1 and concomitantly restored E-cadherin expression. RNA interference-mediated knockdown of HIFalpha in CC-RCC (VHL(-/-)) cells likewise increased E-cadherin expression, while functional hypoxia or expression of VHL mutants incapable of promoting HIFalpha degradation attenuated E-cadherin expression, correlating with the disengagement of RNA polymerase II from the endogenous E-cadherin promoter/gene. These findings reveal a critical HIF-dependent molecular pathway connecting VHL, an established "gatekeeper" of the renal epithelium, with a major epithelial tumor suppressor, E-cadherin. | es |
dc.language.iso | en | es |
dc.publisher | Taylor and Francis Group | es |
dc.title | VHL promotes E2 box-dependent E-cadherin transcription by HIF-mediated regulation of SIP1 and snail | es |
dc.type | article | es |
dc.identifier.doi | https://doi.org/10.1128/MCB.00892-06 | |
dc.issue.number | 1 | es |
dc.journal.title | Molecular and Cellular Biology | es |
dc.page.initial | 157 | es |
dc.page.final | 169 | es |
dc.rights.accessRights | embargoedAccess | es |
dc.subject.area | Biología Celular y Molecular | es |
dc.subject.area | Ciencias Biomédicas | es |
dc.subject.keyword | VHL | es |
dc.subject.keyword | Von Hippel Lindau | es |
dc.subject.keyword | Hypoxia | es |
dc.subject.keyword | HIF | es |
dc.subject.keyword | SNAIL | es |
dc.subject.keyword | SIP1 | es |
dc.subject.keyword | CCRCC | es |
dc.subject.keyword | Cáncer Renal | es |
dc.subject.keyword | E cadherina | es |
dc.subject.unesco | 24 Ciencias de la Vida | es |
dc.volume.number | 27 | es |
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