The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Epstein-Barr Virus Latent Membrane Protein 1 Induces Synthesis of Hypoxia-Inducible Factor 1α
Open accessAbstract
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.
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The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
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Mitochondrial reactive oxygen species trigger hypoxia-induced transcription
Chandel, N. S., Maltepe, E., Goldwasser, E., Mathieu, C. E., Simon, M. C., & Schumacker, P. T. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.20.11715 · Cited by 1,926
Regulation of Mammalian O 2 Homeostasis by Hypoxia-Inducible Factor 1
Semenza, G. L. (1999) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.15.1.551 · Cited by 1,914 · cited 1×
“The specific binding of HIF-1 to the hypoxic response element (HRE) activates the transcription of genes whose products are required for tumor progression, including VEGF, glucose transporters, and insulin-like growth factor 2 ( 48 ).”
BackgroundLaughner, E., Taghavi, P., Chiles, K., Mahon, P. C., & Semenza, G. L. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.12.3995-4004.2001 · Cited by 1,256 · cited 2×
“Laughner et al. showed that overexpression of HER2 increases the rate of HIF-1 protein synthesis that is dependent on the activity of PI3K, Akt, and the downstream kinase, FKBP-rapamycin-associated protein, at the posttranscriptional level in mouse 3T3 cells ( 32 ).”
BackgroundJiang, B. H., Semenza, G. L., Bauer, C., & Marti, H. H. (1996) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1996.271.4.c1172 · Cited by 1,213
Loss of PTEN facilitates HIF-1-mediated gene expression
Zundel, W., Schindler, C., Haas-Kogan, D., Koong, A., Kaper, F., Chen, E., Gottschalk, A. R., Ryan, H. E., Johnson, R. S., Jefferson, A. B., et al. (2000) · Genes & Development · doi:10.1101/gad.14.4.391 · Cited by 840
HIF-1α binding to VHL is regulated by stimulus-sensitive proline hydroxylation
Yu, F., White, S. B., Zhao, Q., & Lee, F. S. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.181341498 · Cited by 796
A Cytoplasmic Inhibitor of the JNK Signal Transduction Pathway
Dickens, M., Rogers, J. S., Cavanagh, J., Raitano, A., Xia, Z., Halpern, J. R., Greenberg, M. E., Sawyers, C. L., & Davis, R. J. (1997) · Science · doi:10.1126/science.277.5326.693 · Cited by 675
Cited by
Integration of Oxygen Signaling at the Consensus HRE
Wenger, R. H., Stiehl, D. P., & Camenisch, G. (2005) · Science's STKE · doi:10.1126/stke.3062005re12 · Cited by 1,032
Interdependence of hypoxic and innate immune responses
Nizet, V., & Johnson, R. S. (2009) · Nature Reviews Immunology · doi:10.1038/nri2607 · Cited by 708
Lactate in the tumour microenvironment: From immune modulation to therapy
Wang, Z.-H., Peng, W.-B., Zhang, P., Yang, X.-P., & Zhou, Q. (2021) · EBioMedicine · doi:10.1016/j.ebiom.2021.103627 · Cited by 528
Dawson, C. W., Port, R. J., & Young, L. S. (2012) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2012.01.004 · Cited by 355
Regulation of Metabolism by Hypoxia-Inducible Factor 1
Semenza, G. L. (2011) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2011.76.010678 · Cited by 342
Metadata
- Authors
- Wakisaka, N., Kondo, S., Yoshizaki, T., Murono, S., Furukawa, M., & Pagano, J. S.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2004-06
- Volume
- 24
- Issue
- 12
- Pages
- 5223-5234
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2110185005
- Cited by
- 204
- References
- 10
- FWCI
- 4.29
- Type
- journal article
- Language
- en
- Open access
- green
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- Wakisaka, N., Kondo, S., Yoshizaki, T., Murono, S., Furukawa, M., & Pagano, J. S. (2004). Epstein-Barr Virus Latent Membrane Protein 1 Induces Synthesis of Hypoxia-Inducible Factor 1α. Molecular and Cellular Biology. https://doi.org/10.1128/mcb.24.12.5223-5234.2004
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