The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
Prolonged Hypoxia Differentially Regulates Hypoxia-inducible Factor (HIF)-1α and HIF-2α Expression in Lung Epithelial Cells
Open accessAbstract
Transcriptional adaptations to hypoxia are mediated by hypoxia-inducible factor (HIF)-1, a heterodimer of HIF-alpha and aryl hydrocarbon receptor nuclear translocator subunits. The HIF-1alpha and HIF-2alpha subunits both undergo rapid hypoxia-induced protein stabilization and bind identical target DNA sequences. When coexpressed in similar cell types, discriminating control mechanisms may exist for their regulation, explaining why HIF-1alpha and HIF-2alpha do not substitute during embryogenesis. We report that, in a human lung epithelial cell line (A549), HIF-1alpha and HIF-2alpha proteins were similarly induced by acute hypoxia (4 h, 0.5% O(2)) at the translational or posttranslational level. However, HIF-1alpha and HIF-2alpha were differentially regulated by prolonged hypoxia (12 h, 0.5% O(2)) since HIF-1alpha protein stimulation disappeared because of a reduction in its mRNA stability, whereas HIF-2alpha protein stimulation remained high and stable. Prolonged hypoxia also induced an increase in the quantity of natural antisense HIF-1alpha (aHIF), whose gene promoter contains several putative hypoxia response elements to which (as we confirm here) the HIF-1alpha or HIF-2alpha protein can bind. Finally, transient transfection of A549 cells by dominant-negative HIF-2alpha, also acting as a dominant-negative for HIF-1alpha, prevented both the decrease in the HIF-1alpha protein and the increase in the aHIF transcript. Taken together, these data indicate that, during prolonged hypoxia, HIF-alpha proteins negatively regulate HIF-1alpha expression through an increase in aHIF and destabilization of HIF-1alpha mRNA. This trans-regulation between HIF-1alpha and HIF-2alpha during hypoxia likely conveys target gene specificity.
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HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O 2 Sensing
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Cited by
HIF1α and HIF2α: sibling rivalry in hypoxic tumour growth and progression
Keith, B., Johnson, R. S., & Simon, M. C. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3183 · Cited by 1,693
Non-coding RNAs as regulators of gene expression and epigenetics
Kaikkonen, M. U., Lam, M. T. Y., & Glass, C. K. (2011) · Cardiovascular Research · doi:10.1093/cvr/cvr097 · Cited by 764
Holmquist-Mengelbier, L., Fredlund, E., Löfstedt, T., Noguera, R., Navarro, S., Nilsson, H., Pietras, A., Vallon-Christersson, J., Borg, Å., Gradin, K., et al. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.08.026 · Cited by 735
Rapid evolution of noncoding RNAs: lack of conservation does not mean lack of function
Pang, K. C., Frith, M. C., & Mattick, J. S. (2006) · Trends in Genetics · doi:10.1016/j.tig.2005.10.003 · Cited by 656
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Metadata
- Authors
- Uchida, T., Rossignol, F., Matthay, M. A., Mounier, R., Couette, S., Clottes, E., & Clerici, C.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2004-04
- Volume
- 279
- Issue
- 15
- Pages
- 14871-14878
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1972783950
- Cited by
- 428
- References
- 36
- FWCI
- 5.51
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Uchida, T., Rossignol, F., Matthay, M. A., Mounier, R., Couette, S., Clottes, E., & Clerici, C. (2004). Prolonged Hypoxia Differentially Regulates Hypoxia-inducible Factor (HIF)-1α and HIF-2α Expression in Lung Epithelial Cells. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m400461200
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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