An Overview Of HIF And Its Role In Hypoxia

Fri, 02/12/2010 - 08:54

Hypoxia-inducible factor (HIF) is a DNA-binding protein that regulates homeostasis via transcription of a wide range of genes. It is inactive in oxygenated cells, but becomes active in hypoxic, i.e. low oxygen conditions. HIF proteins consist of a heterodimeric complex of identical alpha and beta sub-units. The α is degraded in normal oxygen conditions, while the β remains independent of O2 concentration.

HIF is implicated in a wide range of tumours. Recently, we at Novus Biologicals cultured the H1 alpha67 hybridoma cell line to produce the monoclonal anti-HIF 1 alpha antibody. This is one of a number of products in our hypoxia antibody catalogue routinely used in cancer research.

The involvement of HIF-1 in tumour development is obvious when you consider the complexity of the hypoxia pathway. Under normoxic conditions, the α-subunit undergoes prolyl hydroxylation and is tagged by E3 ubiquitin ligase for degradation by the cell proteasome. In hypoxic conditions the α-hydroxylation is inhibited, thus making HIF-1 active. HIF-1 transcriptional activity is not triggered by hypoxia alone; antibody assays have shown that growth factor stimulation of autocrine action, tumour suppressors and increased oncogene activity also promote a hypoxia response. All factor in the potential development of cancer cells.

The genes targeted by HIF proteins enable the cell to survive in a low-oxygen environment, thus preventing cell death. For example, autophagy assays using BNIP antibodies have shown that mitochondrial, rather than whole-cell autophagy is involved. This decreases the cell's requirement for oxygen. However, while the hypoxia response is beneficial during foetal development and ischaemia, it is also implicated in tumourigenesis. Therefore hypoxia antibodies are developed for both normal and carcinoma cell-lines.


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