Prolonged Hypoxia Differentially Regulates Hypoxia-inducible Factor (HIF)-1α and HIF-2α Expression in Lung Epithelial Cells
@article{Uchida2004ProlongedHD, title={Prolonged Hypoxia Differentially Regulates Hypoxia-inducible Factor (HIF)-1$\alpha$ and HIF-2$\alpha$ Expression in Lung Epithelial Cells}, author={Tokujiro Uchida and Fabrice Rossignol and Michael A. Matthay and R{\'e}mi Mounier and Sylvianne Couette and Eric Clottes and Christine Cl{\'e}rici}, journal={Journal of Biological Chemistry}, year={2004}, volume={279}, pages={14871 - 14878} }
Transcriptional adaptations to hypoxia are mediated by hypoxia-inducible factor (HIF)-1, a heterodimer of HIF-α and aryl hydrocarbon receptor nuclear translocator subunits. The HIF-1α and HIF-2α 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-1α and HIF-2α do not substitute during embryogenesis. We report that, in…
360 Citations
Hypoxia upregulates hypoxia inducible factor (HIF)-3α expression in lung epithelial cells: characterization and comparison with HIF-1α
- BiologyCell Research
- 2006
HIF-3α, as a member of the HIF system, is complementary rather than redundant to HIF-1α induction in protection against hypoxic damage in alveolar epithelial cells, according to a variety of activating or inhibitory pharmacological agents.
Cobalt stimulates HIF-1-dependent but inhibits HIF-2-dependent gene expression in liver cancer cells.
- BiologyThe international journal of biochemistry & cell biology
- 2013
Regulation of the HIF-system in human macrophages--differential regulation of HIF-α subunits under sustained hypoxia.
- BiologyMolecular immunology
- 2014
The transition from HIF-1 to HIF-2 during prolonged hypoxia results from reactivation of PHDs and HIF1A mRNA instability
- BiologyCellular & Molecular Biology Letters
- 2022
It is demonstrated that HIF-1 expression is maximal after 4 h of hypoxia in primary endothelial cells and then is dramatically reduced by 8 h, and it is also demonstrated that the alpha mRNA levels directly correlate to the relative alpha protein levels, and therefore to the more stable Hif-2 expression during prolonged Hypoxia.
Hsp70 and CHIP Selectively Mediate Ubiquitination and Degradation of Hypoxia-inducible Factor (HIF)-1α but Not HIF-2α*
- BiologyThe Journal of Biological Chemistry
- 2009
Hsp70- and CHIP-dependent ubiquitination represents a molecular mechanism by which prolonged hypoxia selectively reduces the levels of Hif-1α but not HIF-2α protein.
Recruitment of HIF-1alpha and HIF-2alpha to common target genes is differentially regulated in neuroblastoma: HIF-2alpha promotes an aggressive phenotype.
- BiologyCancer cell
- 2006
REST mediates resolution of HIF-dependent gene expression in prolonged hypoxia
- BiologyScientific reports
- 2015
It is hypothesized that REST represses transcription of Hif-1α in prolonged hypoxia, thus contributing to the resolution of the HIF-1 α response.
Stabilization of Hypoxia-inducible Factor-1α by Prostacyclin under Prolonged Hypoxia via Reducing Reactive Oxygen Species Level in Endothelial Cells*
- BiologyJournal of Biological Chemistry
- 2005
A novel function of PGI2 is demonstrated in down-regulating reactive oxygen species production by attenuating NADPH oxidase activity, which stabilizes HIF-1α in human umbilical vein endothelial cells exposed to prolonged hypoxia.
The HIF-1α antisense long non-coding RNA drives a positive feedback loop of HIF-1α mediated transactivation and glycolysis
- BiologyNature communications
- 2021
The results indicate a critical regulatory role of HIFAL in HIF-1α-driven transactivation and glycolysis, identifying HifAL as a therapeutic target for cancer treatment.
Constitutive/Hypoxic Degradation of HIF-α Proteins by the Proteasome Is Independent of von Hippel Lindau Protein Ubiquitylation and the Transactivation Activity of the Protein*
- BiologyJournal of Biological Chemistry
- 2007
A constitutive, ubiquitin-independent proteasomal degradation pathway of HIF-α proteins has to be taken into account in understanding the biology as well as in the development of therapeutic interventions of highly hypoxic tumors.
References
SHOWING 1-10 OF 37 REFERENCES
Differential Roles of Hypoxia-Inducible Factor 1α (HIF-1α) and HIF-2α in Hypoxic Gene Regulation
- BiologyMolecular and Cellular Biology
- 2003
It is demonstrated that HIF-2α does regulate a variety of broadly expressed hypoxia-inducible genes, suggesting that its function is not restricted, as initially thought, to endothelial cell-specific gene expression.
Up-regulation of hypoxia-inducible factors HIF-1α and HIF-2α under normoxic conditions in renal carcinoma cells by von Hippel-Lindau tumor suppressor gene loss of function
- BiologyOncogene
- 2000
Evidence is provided for a role of the VHL protein in regulation of angiogenesis and erythropoiesis mediated by the HIF-1α and Hif-2α proteins.
Hypoxia-inducible factor-1 alpha is regulated at the post-mRNA level.
- BiologyKidney international
- 1997
The hypoxia-inducible factor-1 (HIF-1) is involved in the induction of oxygen regulated genes such as erythropoietin and vascular endothelial growth factor (VEGF) and there was some variation in Hif-1 alpha mRNA levels, but there did not find significant changes over this time frame, suggesting that HIF- 1 alpha is not transcriptionally regulated.
Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension.
- BiologyProceedings of the National Academy of Sciences of the United States of America
- 1995
Hypoxia-inducible factor 1 (HIF-1) is found in mammalian cells cultured under reduced O2 tension and is necessary for transcriptional activation mediated by the erythropoietin gene enhancer in…
Predominant role of hypoxia-inducible transcription factor (Hif)-1alpha versus Hif-2alpha in regulation of the transcriptional response to hypoxia.
- BiologyCancer research
- 2003
Among a panel of hypoxia-inducible genes, responses were critically dependent on H if-1 alpha but not Hif-2 alpha in both endothelial and breast cancer cells but critically dependent in renal carcinoma cells.
RNA interference for HIF-1alpha inhibits its downstream signalling and affects cellular proliferation.
- BiologyBiochemical and biophysical research communications
- 2003
Hypoxia rapidly activates HIF‐3α mRNA expression
- Biology
- 2003
The results suggest that induction at the transcriptional level is a unique feature of HIF‐3α, which therefore may represent a rapidly reacting component of the HIF system in protection against hypoxic damage.
Cobalt Inhibits the Interaction between Hypoxia-inducible Factor-α and von Hippel-Lindau Protein by Direct Binding to Hypoxia-inducible Factor-α*
- BiologyThe Journal of Biological Chemistry
- 2003
These findings show that cobalt mimics hypoxia, at least in part, by occupying the VHL-binding domain of HIF-α and thereby preventing the degradation of Hif-α.
Induction of endothelial PAS domain protein-1 by hypoxia: characterization and comparison with hypoxia-inducible factor-1alpha.
- BiologyBlood
- 1998
Functional studies in a mutant cell line expressing neither HIF-1alpha nor EPAS-1 confirmed that both proteins interact with hypoxically responsive targets, but suggest target specificity with greater EPas-1 transactivation of the VEGF promoter than the LDH-A promoter.
Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1 alpha.
- BiologyGenes & development
- 1998
It is demonstrated that HIF-1alpha is a master regulator of cellular and developmental O2 homeostasis in Hif1a-/- embryos that manifested neural tube defects, cardiovascular malformations, and marked cell death within the cephalic mesenchyme.