The Tumor Suppressor Mst1 Promotes Changes in the Cellular Redox State by Phosphorylation and Inactivation of Peroxiredoxin-1 Protein |
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Authors: | Sonali Jalan Rawat Caretha L. Creasy Jeffrey R. Peterson Jonathan Chernoff |
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Affiliation: | From the ‡Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111 and ;the §Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102 |
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Abstract: | The serine/threonine protein kinases Mst1 and Mst2 can be activated by cellular stressors including hydrogen peroxide. Using two independent protein interaction screens, we show that these kinases associate, in an oxidation-dependent manner, with Prdx1, an enzyme that regulates the cellular redox state by reducing hydrogen peroxide to water and oxygen. Mst1 inactivates Prdx1 by phosphorylating it at Thr-90 and Thr-183, leading to accumulation of hydrogen peroxide in cells. These results suggest that hydrogen peroxide-stimulated Mst1 activates a positive feedback loop to sustain an oxidizing cellular state. |
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Keywords: | Peroxiredoxin Protein Kinases Redox Signaling Signal Transduction Tumor Suppressor Gene |
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