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Hypoxia-Inducible Factors and Homeostasis

Thu, 09/01/2011 - 09:38

Hypoxia-Inducible Factor-1 (HIF-1) is a highly conserved heterodimeric transcription factor. Novus' antibody catalogue contains an extensive range of both HIF-1 alpha and HIF-1 beta, useful for hypoxia, angiogenesis, cancer and many other areas of research.

The Hypoxia-inducible factors play an essential role in homeostasis, responding to changes in the available oxygen content of the cell. Specifically, they respond to hypoxic, or low oxygen conditions. There are three main members of the human HIF family, each comprising an alpha and beta subunit, encoded by a separate gene. All these proteins are represented in our antibody catalog, which has a particularly extensive range of top quality HIF-1 alpha antibody products.

Immunohistochemistry: HIF Prolyl Hydroxylases Antibody Pack

Much of our knowledge of Hypoxia Inducible Factors is based on studies of HIF-1, which is expressed in practically all oxygen-breathing species. The alpha and beta subunits share a similar tri-domain structure. DNA binding takes place at a bHLH domain on the N-terminus; heterodimerization takes place at a central Per-ARNT-Sim (PAS) domain, and recruitment of transcriptional coregulators is facilitated at the C-terminus.

In normoxic conditions, HIF alpha subunits undergo rapid degradation following hydroxylation by HIF prolyl-hydroxylases, and ubiquitination by VHL E3 ubiquitin ligase. In 2004, HIF-1 alpha antibody research by Semenza, et al. suggested HIF prolyl-hydroxylase utilizes oxygen as a substrate, and is inhibited in hypoxic conditions. Further inhibition occurs as a result of succinate build-up.

Our HIF-1 alpha antibody products may also be of use to drug research groups, and further study in this area is ongoing. Recently, several selective HIF prolyl-hydroxylase inhibitors were developed, for use in oral treatment of anaemia. Inhibition of HIF prolyl-hydroxylase leads to prolonged activity of HIF-1 alpha, resulting in increased levels of erythropoietin.

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