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Inhibitors of the T cell-specific alternative p38 activation pathway and methods of use
Inhibitors of the T cell-specific alternative p38 activation pathway and methods of use
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机译:T细胞特异性p38替代激活途径的抑制剂及其使用方法
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摘要
In T lymphocytes, p38 mitogen activated protein kinase (MAPK) can be activated through an alternative pathway that involves phosphorylation at tyrosine 323. Disclosed herein is the identification of a minimal region of the growth arrest and DNA damage-inducible alpha (Gadd45α) protein that is required for binding to and inhibition of tyrosine 323-phosphorylated p38 in T cells. The disclosed Gadd45α polypeptides inhibit proliferation of T cells in response to T cell receptor stimulation, inhibit differentiation of T cells into Th1 or Th17 cells, inhibit the production of proinflammatory cytokines, and reduce tumor formation and growth of inflammatory cancers, such as pancreatic cancer.
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