The mechanisms involved in the positive regulation of the T cell receptor (TCR)-mediated NFkB activation, and the components of the proximal TCR signaling pathway and the distal IKK portion have been studied at length. However, little is known about the negative regulation of the NFkB pathway in T cells. This negative regulation is crucial in maintaining T cell homeostasis, controlling the duration of TCR signaling, and preventing abnormal lymphocyte activation and proliferation. Therefore, understanding the negative regulation of TCR-mediated NFkB signaling is essential in understanding the mechanisms involved in T cell function and homeostasis. In preliminary studies, we observed that there was an increase in NFkB2/p100 expression upon TCR stimulation with no concomitant increase in p52, the cleavage product of p100. An inhibition in NFkappaB activity upon p100 over-expression and TCR stimulation, and an increase in cell death upon p100 over-expression and anti-Fas antibody stimulation were also observed. Therefore, we will explore the ability of NFkB2/p100 to act as an inhibitory molecule and to participate in the negative regulation of TCR-mediated NF/fB signaling. ? ? ?
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| Friedman, Constantin S; O'Donnell, Marie Anne; Legarda-Addison, Diana et al. (2008) The tumour suppressor CYLD is a negative regulator of RIG-I-mediated antiviral response. EMBO Rep 9:930-6 |
