title: TRAF2 functions as an activator switch in the reactive oxygen species-induced stimulation of MST1.
abstract: Reactive oxygen species (ROS) have many physiological and pathological effects on diverse cellular events. In particular, excessive ROS causes oxidative stress that leads to cell death. The mammalian STE20-like kinase-1 (MST1), a multifunctional serine-threonine kinase, plays a pivotal role in oxidative stress-induced cellular signaling events. Tumor necrosis factor receptor (TNFR)-associated factor 2 (TRAF2) is also known to be essential for oxidative stress-induced cell death. Here, we showed that H2O2 induced the physical interaction between TRAF2 and MST1, and that this interaction promoted the homodimerization as well as the activation of MST1. Furthermore, TRAF2 was required for MST1 to mediate the H2O2-induced stimulation of c-Jun N-terminal kinase and p38 kinase as well as apoptosis. Taken together, our results suggest that TRAF2 functions as a key activator of MST1 in oxidative stress-induced intracellular signaling processes.
authors.affiliation: Laboratory of Cell Death and Human Diseases, Department of Life Sciences, Korea University, Seoul 02841, South Korea.
authors.forename: Kyung-Hye
authors.initials: KH
authors.lastname: Roh
authors.affiliation: Laboratory of Cell Death and Human Diseases, Department of Life Sciences, Korea University, Seoul 02841, South Korea. Electronic address: ejchoi@korea.ac.kr.
authors.forename: Eui-Ju
authors.initials: EJ
authors.lastname: Choi
mesh_terms: D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D017228:Hepatocyte Growth Factor / Q000737:chemistry / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D018345:Mice, Knockout; D018384:Oxidative Stress; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D047992:TNF Receptor-Associated Factor 2 / Q000737:chemistry / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D011518:Proto-Oncogene Proteins; D047992:TNF Receptor-Associated Factor 2; C000622387:TRAF2 protein, mouse; C082332:macrophage stimulating protein; D017228:Hepatocyte Growth Factor; D006861:Hydrogen Peroxide; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Hydrogen peroxide; MST1; Oxidative stress; Reactive oxygen species; TRAF2