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Optical Analysis of Hypoxia Inducible Factor (HIF)-1 Complex Assembly: Imaging of Cellular Oxygen Sensing

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Hypoxia

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 903))

Abstract

Hypoxia is a common phenomenon that occurs in a variety of diseases such as cardiovascular ischemia, anemia, and cancer. Cellular oxygen sensors measure changes in tissue oxygenation and induce responses aimed at restoring sufficient supply with oxygen. Genetic adaptation to hypoxia is under control of hypoxia-inducible factors (HIFs), of which two highly homologous subunits HIF-1α and HIF-2α are regulated by oxygen tension. Together with HIF-1β (=ARNT; aryl hydrocarbon receptor nuclear translocator) they form transcriptionally active complexes under hypoxia which drive the expression of hypoxia inducible genes. The meaning of different HIF complexes, i.e., HIF-1α/ARNT versus HIF-2α/ARNT with respect to target gene or tissue specificity has not been fully resolved. We applied modern microscopic methods like fluorescence resonance energy transfer (FRET) to elucidate protein–protein interactions and fluorescence recovery after photo-bleaching (FRAP) to study mobility of HIF proteins inside the nuclei of living cells. We found differences both in nuclear mobility and the assembly of HIF-1 versus HIF-2 which might help to better understand the assembly of HIF complexes.

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Acknowledgments

Parts of this work were supported by grants from the Deutsche Forschungsgemeinschaft GRK1431 and the Fachhochschule Dortmund.

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Correspondence to Joachim Fandrey .

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Hu, J., Bernardini, A., Fandrey, J. (2016). Optical Analysis of Hypoxia Inducible Factor (HIF)-1 Complex Assembly: Imaging of Cellular Oxygen Sensing. In: Roach, R., Hackett, P., Wagner, P. (eds) Hypoxia. Advances in Experimental Medicine and Biology, vol 903. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-7678-9_17

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