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J Cell Physiol. 2012 Feb;227(2):514-24. doi: 10.1002/jcp.22798.

Functional regulation of HIF-1α under normoxia--is there more than post-translational regulation?

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Department of Sports Medicine, Rehabilitation and Disease Prevention, Johannes-Gutenberg-University Mainz, Germany.


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.

[Indexed for MEDLINE]

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