What is hypoxia inducible factor

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In this respect, advances in gene therapy may allow for a greater ability to directly influence intracellular HIF-1 levels. In the search to find a non-invasive treatment for ischemia, it appears inhibition of 2OG hydroxylases via small molecule therapy is the most promising way to stimulate HIF-1 activity, assuming that selective suppression of such hydroxylases ultimately can be achieved.

Selective inhibition of collagen prolyl hydroxylases [ 7 , 12 ] and in clinical trials of a 2OG-related enzyme, cyclooxygenase II, have been successful [ 50 ]. Suppression of HIF-1 in the treatment of cancer is also a focus, as the significant role of this transcription complex in tumor progression is now recognized [ 15 , 16 , 19 ].

The entire spectrum of HIF-1 function is not yet understood. Accordingly, regulation of transcription factor activation in humans has not yet been achieved. Much remains to learn about the selectivity and properties of factors influencing the HIF-1 pathway [ 51 ]. Despite such gray areas in the knowledge of HIF-1, control of this transcription factor does in fact remain a high-priority target.

Modulation of the HIF-1 pathway promises to have significant effects on cancer and cardiac treatments, potentially affecting the lives of millions who are afflicted with such diseases. National Center for Biotechnology Information , U. Yale J Biol Med. Jennifer E. Ziello , a, b Ion S. Ion S. Author information Copyright and License information Disclaimer.

This is an open access article distributed under the terms of the Creative Commons CC BY-NC license, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited. You may not use the material for commercial purposes. This article has been cited by other articles in PMC. Abstract Hypoxia-Inducible Factor HIF -1 is a dimeric protein complex that plays an integral role in the body's response to low oxygen concentrations, or hypoxia.

Oxygen Metabolism in Mammals Oxygen is required by the cells of most organisms to produce adequate amounts of ATP necessary for metabolic activities. Open in a separate window. Figure 1. Transcriptional Regulation Controls Angiogenesis in Hypoxia One important HIF-1 function is to promote angiogenesis; HIF-1 directs migration of mature endothelial cells toward a hypoxic environment [ 2 , 5 ]. Cancer, Inflammation, and Hypoxia Environments surrounding metastasizing tumor masses are often hypoxic.

Tumor Proliferation Due to its role in hypoxia, HIF-1 plays a critical part in tumor proliferation [ 18 ]. Figure 2. Small Molecule Inhibitors Several small molecules, such as dimethyloxalylglycine, a prolyl hydroxylase inhibitor, activate HIF Therapeutic Targets in the HIF-1 Pathway: Cancer With a clearer understanding of the HIF-1 pathway, efforts are directed at manipulation of this complex genetic process in order to ultimately increase or decrease cellular HIF-1 levels.

Conclusions As more is learned about functions, target genes, and activation pathways of HIF-1, novel treatments of diseases such as cancer and ischemia can be developed. Acknowledgments Dr. References Semenza GL. HIF mediator of physiological and pathophysiological responses to hypoxia.

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