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Int. J. Mol. Sci. 2018, 19(8), 2297; https://doi.org/10.3390/ijms19082297

The Protein Phosphatase PPM1G Destabilizes HIF-1α Expression

1
Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Korea
2
Department of Anatomy and Neurobiology, School of Medicine, Kyung Hee University, Seoul 02447, Korea
3
Department of Pharmacology, School of Medicine, Kyung Hee University, Seoul 02447, Korea
*
Author to whom correspondence should be addressed.
Received: 7 June 2018 / Revised: 23 July 2018 / Accepted: 1 August 2018 / Published: 5 August 2018
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

Hypoxia-inducible factors (HIFs) are key regulators of hypoxic responses, and their stability and transcriptional activity are controlled by several kinases. However, the regulation of HIF by protein phosphatases has not been thoroughly investigated. Here, we found that overexpression of Mg2+/Mn2+-dependent protein phosphatase 1 gamma (PPM1G), one of Ser/Thr protein phosphatases, downregulated protein expression of ectopic HIF-1α under normoxic or acute hypoxic conditions. In addition, the deficiency of PPM1G upregulated protein expression of endogenous HIF-1α under normoxic or acute oxidative stress conditions. PPM1G decreased expression of HIF-1α via the proteasomal pathway. PPM1G-mediated HIF-1α degradation was dependent on prolyl hydroxylase (PHD), but independent of von Hippel-Lindau (VHL). These data suggest that PPM1G is critical for the control of HIF-1α-dependent responses. View Full-Text
Keywords: HIF-1α; PPM1G; hypoxia; normoxia HIF-1α; PPM1G; hypoxia; normoxia
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Pyo, J.; Ryu, J.; Kim, W.; Choi, J.-S.; Jeong, J.-W.; Kim, J.-E. The Protein Phosphatase PPM1G Destabilizes HIF-1α Expression. Int. J. Mol. Sci. 2018, 19, 2297.

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