title: The tumor suppressor Mst1 promotes changes in the cellular redox state by phosphorylation and inactivation of peroxiredoxin-1 protein.
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.
authors: Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111; Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102.
authors: Sonali Jalan
authors: SJ
authors: Rawat
authors: Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
authors: Caretha L
authors: CL
authors: Creasy
authors: Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
authors: Jeffrey R
authors: JR
authors: Peterson
authors: Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111. Electronic address: Jonathan.Chernoff@fccc.edu.
authors: Jonathan
authors: J
authors: Chernoff
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D004249:DNA Damage; D057809:HEK293 Cells; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D054464:Peroxiredoxins / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D000090742:Serine-Threonine Kinase 3; D020798:Two-Hybrid System Techniques; D000099317:Hippo Kinases
chemical_list: D017228:Hepatocyte Growth Factor; D006861:Hydrogen Peroxide; D054464:Peroxiredoxins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000090742:Serine-Threonine Kinase 3; C082332:macrophage stimulating protein; C515940:PRDX1 protein, human; C097835:STK3 protein, human; D000099317:Hippo Kinases
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