Identification and functional characterization of hypoxia-inducible factor 2alpha from the estuarine teleost, Fundulus heteroclitus: interaction of HIF-2alpha with two ARNT2 splice variants

The Journal of Experimental Zoology
Wade H Powell, Mark E Hahn

Abstract

The hypoxia-inducible factors (HIFs) are dimeric transcription factors that mediate changes in gene expression during adaptation of animals to oxygen stress. Both alpha (HIFalpha) and beta (ARNT) subunits are members of the basic helix-loop-helix/Per-ARNT-Sim family of proteins. Mammals have at least three different HIF-alpha subunits, paralogous proteins expressed in tissue-specific fashion (HIF-1alpha, HIF-2alpha, and HIF-3alpha). However, the diversity and functional properties of teleost HIFs are poorly understood. In efforts to characterize mechanisms of hypoxia adaptation in estuarine fish, we have isolated cDNAs encoding HIF subunits from Fundulus heteroclitus (Atlantic killifish or mummichog), including a HIF-2alpha homolog and ARNT2alt, a splice variant of ARNT2 that contains an additional exon encoding 16 amino acids near the amino terminus. HIF-2alpha protein synthesized in vitro binds cognate DNA elements in concert with either Fundulus ARNT2 splice variant or murine ARNT1. HIF-2alpha, ARNT2, and ARNT2alt mRNAs are expressed in all organs examined. The HIF-2alpha cDNA encodes a protein of 96.4 kDa, sharing 53-54% identity with mammalian and avian orthologs. The oxygen-dependent degradation domain, however, exhibits ...Continue Reading

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Aug 6, 2002·Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology·Mikko Nikinmaa
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