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Publication : p38 mitogen-activated protein kinase mediates the Fas-induced mitochondrial death pathway in CD8+ T cells.

First Author  Farley N Year  2006
Journal  Mol Cell Biol Volume  26
Issue  6 Pages  2118-29
PubMed ID  16507991 Mgi Jnum  J:106915
Mgi Id  MGI:3619769 Doi  10.1128/MCB.26.6.2118-2129.2006
Citation  Farley N, et al. (2006) p38 mitogen-activated protein kinase mediates the Fas-induced mitochondrial death pathway in CD8+ T cells. Mol Cell Biol 26(6):2118-29
abstractText  The p38 mitogen-activated protein kinase (MAPK) signaling pathway can be activated by a variety of stress stimuli such as UV radiation and osmotic stress. The regulation and role of this pathway in death receptor-induced apoptosis remain unclear and may depend on the specific death receptor and cell type. Here we show that binding of Fas ligand to Fas activates p38 MAPK in CD8+ T cells and that activation of this pathway is required for Fas-mediated CD8+ T-cell death. Active p38 MAPK phosphorylates Bcl-xL and Bcl-2 and prevents the accumulation of these antiapoptotic molecules within the mitochondria. Consequently, a loss of mitochondrial membrane potential and the release of cytochrome c lead to the activation of caspase 9 and, subsequently, caspase 3. Therefore, the activation of p38 MAPK is a critical link between Fas and the mitochondrial death pathway and is required for the Fas-induced apoptosis of CD8+ T cells.
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