Signals transducers and activators of transcription (STAT)-induced STAT inhibitor-1 (SSI-1)/suppressor of cytokine signaling-1 (SOCS-1) suppresses tumor necrosis …

Y Morita, T Naka, Y Kawazoe… - Proceedings of the …, 2000 - National Acad Sciences
Y Morita, T Naka, Y Kawazoe, M Fujimoto, M Narazaki, R Nakagawa, H Fukuyama…
Proceedings of the National Academy of Sciences, 2000National Acad Sciences
Signal transducers and activators of transcription (STAT)-induced STAT inhibitor-1 [SSI-1;
also known as suppressor of cytokine signaling-1 (SOCS-1)] was identified as a negative
feedback regulator of Janus kinase-STAT signaling. We previously generated mice lacking
the SSI-1 gene (SSI-1−/−) and showed that thymocytes and splenocytes in SSI-1−/− mice
underwent accelerated apoptosis. In this paper, we show that murine embryonic fibroblasts
lacking the SSI-1 gene are more sensitive than their littermate controls to tumor necrosis …
Signal transducers and activators of transcription (STAT)-induced STAT inhibitor-1 [SSI-1; also known as suppressor of cytokine signaling-1 (SOCS-1)] was identified as a negative feedback regulator of Janus kinase-STAT signaling. We previously generated mice lacking the SSI-1 gene (SSI-1 −/−) and showed that thymocytes and splenocytes in SSI-1 −/− mice underwent accelerated apoptosis. In this paper, we show that murine embryonic fibroblasts lacking the SSI-1 gene are more sensitive than their littermate controls to tumor necrosis factor-α (TNF-α)-induced cell death. In addition, L929 cells forced to express SSI-1 (L929/SSI-1), but not SSI-3 or SOCS-5, are resistant to TNF-α-induced cell death. Furthermore L929/SSI-1 cells treated with TNF-α sustain the activation of p38 mitogen-activated protein (MAP) kinase. In contrast, SSI-1 −/− murine embryonic fibroblasts treated with TNF-α show hardly any activation of p38 MAP kinase. These findings suggest that SSI-1 suppresses TNF-α-induced cell death, which is mediated by p38 MAP kinase signaling.
National Acad Sciences