1. Subcellular localization and regulation of hypoxia-inducible factor-2α in vascular endothelial cells
- Author
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Yoshihito Nakatani, Chie Kobayashi, Manabu Kunimoto, Ichiro Kudo, Ryo Takahashi, Shuntaro Hara, Nobumasa Imura, and Yukihiro Kondo
- Subjects
Aryl hydrocarbon receptor nuclear translocator ,Transcription, Genetic ,Molecular Sequence Data ,Biophysics ,Biology ,Response Elements ,Transfection ,Biochemistry ,Xenobiotics ,Gene expression ,Basic Helix-Loop-Helix Transcription Factors ,Animals ,Amino Acid Sequence ,Luciferases ,Molecular Biology ,Transcription factor ,G alpha subunit ,Regulation of gene expression ,Aryl Hydrocarbon Receptor Nuclear Translocator ,Arteries ,Cell Biology ,Hypoxia-Inducible Factor 1, alpha Subunit ,Subcellular localization ,Molecular biology ,Cell Hypoxia ,Cell biology ,DNA-Binding Proteins ,Repressor Proteins ,Gene Expression Regulation ,Receptors, Aryl Hydrocarbon ,Hypoxia-inducible factors ,Cattle ,Endothelium, Vascular ,Subcellular Fractions ,Transcription Factors - Abstract
The hypoxia-inducible factors 1alpha (HIF-1alpha) and 2alpha (HIF-2alpha) have extensive structural homology and have been identified as transcription factors that mediate hypoxia-inducible gene expression through hypoxia-responsive element (HRE). They play critical roles not only in normal development, but also in tumor progression. Endothelial cells (EC) express both HIF-1alpha and -2alpha. In this study, we examined the subcellular localization of HIF-1alpha and -2alpha in bovine arterial EC (BAEC) by immunoblotting and immunocytostaining analysis and found that even under normoxic conditions, as with its heterodimeric partner ARNT, HIF-2alpha was stable, and was localized in the nucleus of BAEC differently than HIF-1alpha. HIF-2alpha might be regulated by a different mechanism than HIF-1alpha and might mediate the expression of some EC-specific genes under normoxic conditions. We further found that cardiovascular helix-loop-helix factor (CHF) 2, which had been identified as an ARNT-interacting protein, was expressed in BAEC and suppressed HRE-dependent gene expression both under normoxia and hypoxia. CHF2 might be one of the key regulators of HIF-2alpha-mediated gene expression in normoxic EC.
- Published
- 2004