Journal of Biological Chemistry · 2013 · 63 citations · 35 references
Life SciencesBiochemistryCell BiologyCarcinogenesisMolecular OncologyRedox BiochemistryCancer Cell SignalingCellular Redox HomeostasisPeroxiredoxin BiologyRedox SignalingTumor Suppressor Gene InactivationTumor Suppressor GenesCellular Redox BalanceCellular Redox ImbalanceCellular Redox SignalingPeroxiredoxin SystemReactive Oxygen Species RegulationTumor Suppressor LossTumor Suppressor Pathways
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. 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.
35