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Degradation of the Hypoxia-Inducible Factor 1α, Where Does it Happen?

Teresa Pereira, Xiaowei Zheng and Lorenz Poellinger

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Adaptive responses to hypoxia are essential for the survival of all organisms. Under hypoxic conditions, the transcription of a large group of genes relevant for oxygen homeostasis is induced by the hypoxia-inducible factor-1 (HIF-1). These genes encode proteins that enable the cells to adapt to limiting oxygen levels by increasing oxygen delivery through induction of angiogenesis or erythopoiesis and producing ATP under anerobic conditions. The stability of HIF-1α protein is also target of O₂ regulation. At normoxia HIF-1α is hydroxylated at specific proline residues by a recently identified family of prolyl hydroxyalses. Hydroxylated HIF-1α is recognized by the Von Hippel-Lindau tumor suppressor gene product (pVHL) as an ubiquitylation substrate that leads to proteasomal-dependent degradation of HIF-1α. We have recently demonstrated that the major subcellular compartment where degradation of HIF-1α occurs is dependent on the levels of proteosomal activity and on the localization of HIF-1α. Furthermore we have shown that the localization of HIF-1α degradation is a cell type-characteristic parameter. These observations indicate new levels of complexity in the regulation of HIF-1α degradation.

Authors

Teresa Pereira

Karolinska Institute, Stockholm, Sweden

Xiaowei Zheng

Karolinska Institute, Stockholm, Sweden

Lorenz Poellinger

Karolinska Institute, Stockholm, Sweden

This is an open-access article

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.