The tumor suppressor Mst1 promotes changes in the cellular redox state by phosphorylation and inactivation of peroxiredoxin-1 protein

Sonali Jalan Rawat, Caretha L. Creasy, Jeffrey R. Peterson, Jonathan Chernoff

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

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.

Original languageEnglish
Pages (from-to)8762-8771
Number of pages10
JournalJournal of Biological Chemistry
Volume288
Issue number12
DOIs
StatePublished - Mar 22 2013

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