SOCS-1 suppresses TNF- -induced apoptosis through the regulation of Jak activation

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Abstract
Suppressor of cytokine signaling‐1 (SOCS‐1) was identified as one of the negative feedback regulators of Janus kinase (Jak)‐signal‐transducer‐and‐activator‐of‐transcription (STAT) signaling. So far, it has been reported that SOCS‐1 inhibits the action of multiple cytokines at least in vitro. We previously showed that SOCS‐1 suppresses tumor necrosis factor‐α (TNF‐α)‐induced apoptosis in murine embryonic fibroblast, but the mechanism of suppression was not fully clarified. In this study, we show that Jaks bind to TNF receptor‐1 (TNFR‐1) and are activated by TNF‐α. We also show that the activations of Jaks and caspases by TNF‐α are suppressed by SOCS‐1. Furthermore, in Jak‐deficient cell lines, DNA fragmentation and caspase‐8 activation by TNF‐α are suppressed, indicating that Jaks participate in TNF‐α‐induced apoptosis signaling. Taken together, these results suggest that SOCS‐1 inhibits TNF‐α‐induced apoptosis through regulation of Jaks.

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