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• W2110185005 endingPage "5234" @default.
• W2110185005 startingPage "5223" @default.
• W2110185005 abstract "Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric basic helix-loop-helix transcription factor composed of HIF-1 alpha and HIF-1 beta that is the central regulator of responses to hypoxia. The specific binding of HIF-1 to the hypoxia-responsive element (HRE) induces the transcription of genes that respond to hypoxic conditions, including vascular endothelial growth factor (VEGF). Here we report that expression of HIF-1 alpha is increased in diverse Epstein-Barr virus (EBV)-infected type II and III cell lines, which express EBV latent membrane protein 1 (LMP1), the principal EBV oncoprotein, as well as other latency proteins, but not in the parental EBV-negative cell lines. We show first that transfection of an LMP1 expression plasmid into Ad-AH cells, an EBV-negative nasopharyngeal epithelial cell line, induces synthesis of HIF-1 alpha protein without increasing its stability or mRNA level. The mitogen-activated protein kinase (MAPK) kinase inhibitor PD98059 markedly reduces induction of HIF-1 alpha by LMP1. Catalase, an H(2)O(2) scavenger, strongly suppresses LMP1-induced production of H(2)O(2), which results in a decrease in the expression of HIF-1 alpha induced by LMP1. Inhibition of the NF-kappa B, c-jun N-terminal kinase, p38 MAPK, and phosphatidylinositol 3-kinase pathways did not affect HIF-1 alpha expression. Moreover, LMP1 induces HIF-1 DNA binding activity and upregulates HRE and VEGF promoter transcriptional activity. Finally, LMP1 increases the appearance of VEGF protein in extracellular fluids; induction of VEGF is suppressed by PD98059 or catalase. These results suggest that LMP1 increases HIF-1 activity through induction of HIF-1 alpha protein expression, which is controlled by p42/p44 MAPK activity and H(2)O(2). The ability of EBV, and specifically its major oncoprotein, LMP1, to induce HIF-1 alpha along with other invasiveness and angiogenic factors reported previously discloses additional oncogenic properties of this tumor virus." @default.
• W2110185005 created "2016-06-24" @default.
• W2110185005 creator A5018497343 @default.
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• W2110185005 creator A5075719027 @default.
• W2110185005 creator A5090455609 @default.
• W2110185005 creator A5090897933 @default.
• W2110185005 date "2004-06-01" @default.
• W2110185005 modified "2023-10-05" @default.
• W2110185005 title "Epstein-Barr Virus Latent Membrane Protein 1 Induces Synthesis of Hypoxia-Inducible Factor 1α" @default.
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• W2110185005 doi "https://doi.org/10.1128/mcb.24.12.5223-5234.2004" @default.
• W2110185005 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/419879" @default.
• W2110185005 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/15169887" @default.
• W2110185005 hasPublicationYear "2004" @default.
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