HIF-1α (C-Term) Monoclonal Antibody (Clone 8B12)

Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor subunit that belongs to the basic helix-loop-helix PER-ARNT-SIM (bHLH-PAS) protein family.^1,2 It contains bHLH and PAS domains that mediate DNA binding and heterodimerization with the HIF-1β subunit, an oxygen-dependent degradation (ODD) domain that is hydroxylated by prolyl hydroxylase in the presence of oxygen to target HIF-1α for proteasomal degradation, and N- and C-terminal transactivation domains responsible for regulating the expression of HIF-1 target genes.^2,3 Under hypoxic conditions, HIF-1α is stabilized, accumulates in the cytoplasm, and is translocated to the nucleus where it forms a heterodimer with HIF-1β and induces the expression of genes involved in maintaining cellular oxygen homeostasis.^2,4,1,5 It is also involved in angiogenesis, glucose utilization, and pH regulation under hypoxic conditions, including in the tumor microenvironment.⁶ HIF-1α is overexpressed in a variety of cancer cell lines where it promotes survival of cancer cells and increases invasiveness under hypoxic conditions and, in vivo, overexpression is associated with aggressiveness and progression of various cancers and poor disease-free survival.^7,8,6,9 Homozygous knockout of HIF-1α is embryonic lethal due to disruptions in vascular development but conditional knockout models have demonstrated a role for HIF-1α in inflammation, immunity, and osteogenesis.⁶ Cayman’s HIF-1α Monoclonal Antibody can be used for Western blot and immunocytochemistry applications. The antibody recognizes HIF-1α at 93 kDa from human and mouse samples.

WARNING This product is not for human or veterinary use.

1. Wang, G.L., Jiang, B.H., Rue, E.A., et al. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O₂ tension. Proc. Natl. Acad. Sci. USA 92(12), 5510-5514 (1995).

2. Bhattarai, D., Xu, X., and Lee, K. Hypoxia-inducible factor-1 (HIF-1) inhibitors from the last decade (2007 to 2016): A "structure-activity relationship" perspective. Med. Res. Rev. 38(4), 1404-1442 (2018).

3. Li, J., Xi, W., Li, X., et al. Advances in inhibition of protein-protein interactions targeting hypoxia-inducible factor-1 for cancer therapy. Bioorg. Med. Chem. 27(7), 1145-1158 (2019).

4. Wenger, R.H. Cellular adaptation to hypoxia: O₂-sensing protein hydroxylases, hypoxia-inducible transcription factors, and O₂ regulated gene expression. FASEB J. 16(10), 1151-1162 (2002).

5. Safran, M., and Kaelin, W.G., Jr. HIF hydroxylation and the mammalian oxygen-sensing pathway. J. Clin. Invest. 111(6), 779-783 (2003).

6. Weidemann, A., and Johnson, R.S. Biology of HIF-1α. Cell Death Differ. 15(4), 621-627 (2008).

7. Talks, K.L., Turley, H., Gatter, K.C., et al. The expression and distribution of the hypoxia-inducible factors HIF-1α and HIF-2α in normal human tissues, cancers, and tumor-associated macrophages. Am. J. Pathol. 157(2), 411-421 (2000).

8. Choi, J.Y., Jang, Y.S., Min, S.Y., et al. Overexpression of MMP-9 and HIF-1α in breast cancer cells under hypoxic conditions. J. Breast Cancer 14(2), 88-95 (2011).

9. Chen, L., Shi, Y., Yuan, J., et al. HIF-1 alpha overexpression correlates with poor overall survival and disease-free survival in gastric cancer patients post-gastrectomy. PLoS One 9(3), e90678 (2014).