Hypoxia-induced factor

The hypoxia-induced factor, or HIF for short, is a transcription factor complex that regulates the supply of oxygen to the cell by creating a balance between oxygen demand and oxygen supply. The coding gene (gene name: HIF1A) is located on the gene 14: 61.23 - 61.28. The protein HIF consists of a labile alpha subunit, which exists in humans (and mice) in three isoforms, HIF-1 -3alpha, and a beta subunit.

If an O2 deficiency occurs in a cell, the cells respond to this condition by activating selected genes under the control of the transcription factor complex "hypoxia inducible factor-1" HIF-1. A subcutaneous layer of HIF (HIF-1alpha) is pO2-sensitive.

HIF-1alpha is continuously synthesized, but if the cell's pO2 is high or normal, it is degraded within minutes via the Hippel-Lindau tumor suppressor protein. In a hypoxemic state, however, HIF-1alpha is stabilized, accumulates and can translocate into the nucleus. HIF activates the erythropoietin gene (erythropoietin formation) and a number of other genes.

HIF-1 is regulated by post-translational hydroxylation of its alpha-subunit, whereby both the amount and the activity of HIF-1 are controlled by the oxygen concentration in the cell. The enzymes responsible for this modification, prolyl and asparaginyl hydroxylases, serve as cellular oxygen sensors.

HIF-1 plays a central role not only in the physiological response of cells to hypoxia, but also in the pathophysiology of ischemic tissue and the tumor microenvironment. The HIF-1 target genes identified so far can be divided into two groups:

• genes whose products provide ATP by increasing anaerobic glucose degradation
• Genes whose products improve tissue oxygenation through increased vascularization, vascular dilatation or by increasing erythropoiesis. Furthermore, it is assumed that HIF-induced expression of VEGF (vascular endothelial growth factor) and GLUT-1 (glucose transporter type 1) occurs.

Overexpression of HIF plays a role in hereditary leiomyomatosis .

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