title: The p38 pathway regulates oxidative stress tolerance by phosphorylation of mitochondrial protein IscU.
abstract: 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.
authors.affiliation: State Key Laboratory of Cellular Stress Biology and School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Tian
authors.affiliation: Key Laboratory of Marine Biogenetic Resources, Third Institute of Oceanography, State Oceanic Administration (SOA), Xiamen, Fujian 361005, China, and. Electronic address: chenjm@xmu.edu.cn.
authors.forename: Jianming
authors.initials: J
authors.lastname: Chen
authors.affiliation: Key Laboratory of Marine Biogenetic Resources, Third Institute of Oceanography, State Oceanic Administration (SOA), Xiamen, Fujian 361005, China, and.
authors.forename: Mingliang
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Physiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Chloe
authors.initials: C
authors.lastname: Gui
authors.affiliation: State Key Laboratory of Cellular Stress Biology and School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.
authors.forename: Chuan-Qi
authors.initials: CQ
authors.lastname: Zhong
authors.affiliation: State Key Laboratory of Cellular Stress Biology and School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Hong
authors.affiliation: State Key Laboratory of Cellular Stress Biology and School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.
authors.forename: Changchuan
authors.initials: C
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Cellular Stress Biology and School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.
authors.forename: Xiurong
authors.initials: X
authors.lastname: Wu
authors.affiliation: Key Laboratory of Marine Biogenetic Resources, Third Institute of Oceanography, State Oceanic Administration (SOA), Xiamen, Fujian 361005, China, and.
authors.forename: Lirong
authors.initials: L
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Cellular Stress Biology and School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.
authors.forename: Vakil
authors.initials: V
authors.lastname: Ahmad
authors.affiliation: State Key Laboratory of Cellular Stress Biology and School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.
authors.forename: Jiahuai
authors.initials: J
authors.lastname: Han
mesh_terms: D000154:Aconitate Hydratase / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D042967:Electron Transport Complex I / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D007506:Iron-Sulfur Proteins / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D018384:Oxidative Stress; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D000099190:MAP-Kinase-Activated Kinase 2
chemical_list: D000154:Aconitate Hydratase; D029721:Drosophila Proteins; D042967:Electron Transport Complex I; D047908:Intracellular Signaling Peptides and Proteins; D007506:Iron-Sulfur Proteins; D024101:Mitochondrial Proteins; D017346:Protein Serine-Threonine Kinases; D000099190:MAP-Kinase-Activated Kinase 2; C506160:ISCU protein, human; C000594608:IscU protein, Drosophila
keywords: Iron-Sulfur Protein; Mitochondrial Aconitase; Oxidative Stress; p38; p38 MAPK