Functional regulation of HIF-1α under normoxia—is there more than post-translational regulation?
✍ Scribed by A. Kuschel; P. Simon; S. Tug
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 216 KB
- Volume
- 227
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
Abstract
The hypoxia‐inducible factor‐1 (HIF‐1) is an oxygen‐regulated transcriptional activator playing a pivotal role in mammalian physiology and disease pathogenesis, e.g., HIF‐1 is indispensable in a broad range of developmental stages in different tumors. Its post‐translational regulation via PHDs under the influence of hypoxia is widely investigated and accepted. Different non‐hypoxic stimuli such as lipopolysaccharides (LPS), thrombin, and angiotensin II (Ang II), have been proven to enhance HIF‐1 levels through activation of regulative mechanisms distinct from protein stabilization. Some of these stimuli specifically regulate HIF‐1α at the transcriptional, post‐transcriptional, or translational level, whereas others additionally influence post‐translational modifications. Thus, it is difficult for the investigators to discern the impact of the different mechanisms leading to functional HIF‐1 protein. Nevertheless, profound knowledge of additional regulatory networks appears to depict new therapeutic opportunities and thus is an interesting and important field for further investigations. J. Cell. Physiol. 227: 514–524, 2012. © 2011 Wiley Periodicals, Inc.