The p38 pathway regulates oxidative stress tolerance by phosphorylation of mitochondrial protein IscU.
The p38 pathway is an evolutionarily conserved signaling pathway that responds to a variety of stresses. However, the underlying mechanisms are largely unknown. In the present study, we demonstrate that p38b is a major p38 MAPK involved in the regulation of oxidative stress tolerance in addition to p38a and p38c ... in Drosophila. We further show the importance of MK2 as a p38-activated downstream kinase in resistance to oxidative stresses. Furthermore, we identified the iron-sulfur cluster scaffold protein IscU as a new substrate of MK2 both in Drosophila cells and in mammalian cells. These results imply a new mechanistic connection between the p38 pathway and mitochondria iron-sulfur clusters.
Mesh Terms:
Aconitate Hydratase, Amino Acid Sequence, Animals, Animals, Genetically Modified, Drosophila Proteins, Drosophila melanogaster, Electron Transport Complex I, Gene Expression Regulation, Enzymologic, HEK293 Cells, Humans, Intracellular Signaling Peptides and Proteins, Iron-Sulfur Proteins, MAP Kinase Signaling System, Mitochondrial Proteins, Molecular Sequence Data, Oxidative Stress, Phosphorylation, Protein Binding, Protein-Serine-Threonine Kinases, Sequence Homology, Amino Acid
Aconitate Hydratase, Amino Acid Sequence, Animals, Animals, Genetically Modified, Drosophila Proteins, Drosophila melanogaster, Electron Transport Complex I, Gene Expression Regulation, Enzymologic, HEK293 Cells, Humans, Intracellular Signaling Peptides and Proteins, Iron-Sulfur Proteins, MAP Kinase Signaling System, Mitochondrial Proteins, Molecular Sequence Data, Oxidative Stress, Phosphorylation, Protein Binding, Protein-Serine-Threonine Kinases, Sequence Homology, Amino Acid
J. Biol. Chem.
Date: Nov. 14, 2014
PubMed ID: 25204651
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