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- W2105891541 abstract "Hypoxia-inducible factor 1 (HIF1) is up-regulated in most malignant tumors usually via interruption of ubiquitination and proteasomal degradation of its subunit alpha. Recently, we have shown that the principal EBV oncoprotein, latent membrane protein 1 (LMP1), activates HIF1alpha and subsequently expression of HIF1-responsive genes in epithelial cells. Here, we explore the mechanism for HIF1alpha activation by LMP1 in nasopharyngeal epithelial cells: LMP1 up-regulates the level of Siah1 E3 ubiquitin ligase by enhancing its stability, which subsequently induces proteasomal degradation of prolyl HIF-hydroxylases 1 and 3 that normally mark HIF1alpha for degradation. As a result, LMP1 prevents formation of von Hippel-Lindau/HIF1alpha complex, as shown by coimmunoprecipitation analyses. Thus, Siah1 is implicated in the regulation of HIF1alpha and is involved in a recently appreciated aspect of EBV-mediated tumorigenesis, namely, the angiogenesis process triggered by LMP1." @default.
- W2105891541 created "2016-06-24" @default.
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- W2105891541 date "2006-10-15" @default.
- W2105891541 modified "2023-10-09" @default.
- W2105891541 title "EBV Latent Membrane Protein 1 Up-regulates Hypoxia-Inducible Factor 1α through Siah1-Mediated Down-regulation of Prolyl Hydroxylases 1 and 3 in Nasopharyngeal Epithelial Cells" @default.
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- W2105891541 doi "https://doi.org/10.1158/0008-5472.can-06-1679" @default.
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