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The MAPK p38c Regulates Oxidative Stress and Lipid Homeostasis in the Intestine


The p38 mitogen-activated protein (MAP) kinase is a signaling pathway that is involved in both stress and immunity in various species from yeast to human. p38 kinases regulate transcription factors of the ATF family and other protein kinases that then induce cellular adaptation to stress to a wide variety of physical, chemical and biological stresses. The Drosophila genome encodes three p38 kinases named p38a, p38b and p38c. In this study, we have analyzed the role of p38c in the Drosophila intestine. The p38c gene is expressed in the digestive tract and up-regulated upon intestinal infection. We observed a lower production of Reactive Oxygen Species (ROS) in the gut of p38c mutants upon bacterial infection. Consistent with this observation, the transcription of the Duox, a gene encoding an enzyme that produces ROS, is reduced in p38c mutant flies. Our analysis shows that p38c induces the phosphorylation of Atf-2, a transcription factor that controls Duox expression. Interestingly, our study also shows that p38c and Atf3 function in a common pathway in the intestine to regulate lipid metabolism and immune homeostasis. Collectively, our study demonstrates that p38c plays a central role in the intestine of Drosophila.


Vyšlo v časopise: The MAPK p38c Regulates Oxidative Stress and Lipid Homeostasis in the Intestine. PLoS Genet 10(9): e32767. doi:10.1371/journal.pgen.1004659
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004659

Souhrn

The p38 mitogen-activated protein (MAP) kinase is a signaling pathway that is involved in both stress and immunity in various species from yeast to human. p38 kinases regulate transcription factors of the ATF family and other protein kinases that then induce cellular adaptation to stress to a wide variety of physical, chemical and biological stresses. The Drosophila genome encodes three p38 kinases named p38a, p38b and p38c. In this study, we have analyzed the role of p38c in the Drosophila intestine. The p38c gene is expressed in the digestive tract and up-regulated upon intestinal infection. We observed a lower production of Reactive Oxygen Species (ROS) in the gut of p38c mutants upon bacterial infection. Consistent with this observation, the transcription of the Duox, a gene encoding an enzyme that produces ROS, is reduced in p38c mutant flies. Our analysis shows that p38c induces the phosphorylation of Atf-2, a transcription factor that controls Duox expression. Interestingly, our study also shows that p38c and Atf3 function in a common pathway in the intestine to regulate lipid metabolism and immune homeostasis. Collectively, our study demonstrates that p38c plays a central role in the intestine of Drosophila.


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