Summary
Hypoxia-inducible factor-1 (HIF-1) is a master regulator of mammalian oxygen homeostasis. HIF-1 consists of two subunits, HIF-1α and the aryl hydrocarbon receptor nuclear translocator (ARNT). Whereas hypoxia prevents ubiquitination and proteasomal degradation of HIF-1α ARNT expression is thought to be oxygen-independent. We and others previously showed that ARNT is indispensable for HIF-1 DNA-binding and transactivation function. To examine the requirement of ARNT for accumulation and nuclear translocation of HIF-1α in hypoxia, we used ARNT-mutant mouse hepatoma and ARNT-deficient embryonic stem cells. As shown by immunofluorescence, HIF-1α accumulation in the nucleus of hypoxic cells did not require ARNT, demonstrating that nuclear translocation is intrinsic to HIF-1α During biochemical separation, both HIF-1α and ARNT tend to leak from the nuclei in the absence of the corresponding subunit, suggesting that heterodimerization is required for stable association within the nuclear compartment. Nuclear stabilization of the heterodimer might also explain the hypoxically increased total cellular ARNT levels observed in some of the cell lines examined.
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Gassmann, M., Chilov, D., Wenger, R.H. (2002). Regulation of the Hypoxia-Inducible Factor-1α. In: Lahiri, S., Prabhakar, N.R., Forster, R.E. (eds) Oxygen Sensing. Advances in Experimental Medicine and Biology, vol 475. Springer, Boston, MA. https://doi.org/10.1007/0-306-46825-5_9
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