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Cardiovascular & Hematological Agents in Medicinal Chemistry

Eiditor-in-Chief

ISSN (Print): 1871-5257
ISSN (Online): 1875-6182

Hypoxia-inducible Factor (HIF) in Hormone Signaling During Health and Disease

Author(s): Nathalie Dehne, Dominik Fuhrmann and Bernhard Brune

Volume 11 , Issue 2 , 2013

Page: [125 - 135] Pages: 11

DOI: 10.2174/1871525711311020008

Price: $58

Abstract

Hypoxia-inducible factor (HIF) is a dimeric transcription factor identified as the major regulator of hypoxic responses in cells. Its activity is mainly regulated by protein stability. In well-oxygenated tissues prolyl hydroxylases hydroxylate HIF-1α and HIF-2α protein to provoke their proteasomal degradation. Under hypoxia the α-subunits are stabilized and dimerize with ß-subunits to constitute active transcriptional complexes. As the α-subunits are constantly translated and degraded, any interference with cellular translation will alter HIF-α expression and HIF activity. Cytokines such as interleukins or interferons as well as growth factors such as vascular endothelial growth factor or insulin-like growth factor are good examples of hormones that affect transcription, translation, or degradation of HIF-1α. In turn, HIF specific target genes also modulate the expression and/or signaling quality of cytokines or growth factors to create signal amplifying/intercepting cellular networks. We define how these signaling circuits promote or delay the progression of diseases and describe potential outcomes for patients.

Keywords: Hypoxia-inducible factor, cancer, insulin, insulin-like growth factor, interferon, interleukin, mTOR, tumor necrosis factor, vascular endothelial growth factor.


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