An Overview of Hypoxia

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The hypoxic response pathway is activated as a result of low levels of oxygen within the cellular environment, and the hypoxia inducible transcription factor, known as HIF, is fundamental to the hypoxic response. Hypoxia signaling dysregulation is commonly found in tumor angiogenesis – where current research is focused on renal cell carcinoma and the role of HIF2-alpha – chronic inflammation, and cardiovascular diseases. HIF was originally identified as a factor that bound to the hypoxia-response element (HRE) located in the promoter of the erythropoietin gene. HIF has since been found to associate with a number of promoters and regulate gene expression in response to the stress of low oxygen.

HIF exists as a heterodimeric transcription factor composed of an alpha and beta subunit. The HIF-alpha and HIF-beta subunits are similar in structure and are members of the basic helix-loop-helix (bHLH)-containing PERF-ARNT-SIM (PAS) domain family of transcription factors. In mammals there are 3 genes that encode HIF-alpha subunits, HIF1-alpha, HIF2-alpha, and HIF3-alpha. Under conditions of normoxia, HIF-alpha subunits are constitutively expressed and rapidly degraded via ubiquitination and proteasome activity mediated by the von-Hippel-Landau (pVHL) tumor suppressor (a component of a multisubunit ubiqutin-protein ligase complex). Recognition of HIF-alpha by pVHL during normoxic conditions is mediated by hydroxylation of proline and asparagine residues on HIF-alpha. The Hydroxylation of HIF-alpha is catalyzed by the FIH-1 asparaginyl hydroxylase and four paralogous prolyl hydroxylases: EGLN1/PHD2, EGLN2/PHD1, EGLN3/PHD3 and PHD4. During hypoxia, pVHL does not recognize HIF-alpha, causing it to become stabilized and to accumulate in the cell where it dimerizes with the beta subunit and coactivators such as CBP/p300 in the nucleus to activate gene transcription from HREs. It appears that oxygen regulates HIF activity via several mechanisms. Oxygen-independent mechanisms also exist, suggesting that the regulation of HIF is both complex and multilayered.


Detection of human HIF2-alpha (red) in formaldehyde-fixed asynchronous HepG2 cells.

Detection of human HIF2-alpha (red) in formaldehyde-fixed asynchronous HepG2 cells untreated (left) and treated with CoCI2 (right) by ICC-IF. Antibody: Rabbit anti-HIF2-alpha recombinant monoclonal [BL-95-1A2] (A700-003). Secondary: DyLight® 594-conjugated goat anti-rabbit IgG (A120-201D4). Counterstain: DAPI (blue).

Detection of human HdmX/MDM4 by WB of Jurkat lysate

Detection of human HdmX/MDM4 by WB of Jurkat lysate. Antibody: Rabbit anti-HdmX/MDM4 recombinant monoclonal [BL-3.2F2] (A700-000). Secondary: HRP-conjugated goat anti-rabbit IgG (A120-101P).



Below is the entire list of targets involved with hypoxia. Can’t find what you are looking for? Bethyl offers a custom antibody service.