A Key Role for NF-κB Transcription Factor c-Rel in T-Lymphocyte-Differentiation and Effector Functions
Figure 1
Canonical and alternative NF-κB activation pathways in T cells. Several signals are required for the activation of the canonical NF-κB-signalling pathway. The inhibitory IκB proteins typically bind to dimers of the NF-κB family such as p65/p50 (not shown in the figure) and c-Rel/p50 to generate inactive complexes that are sequestered in the cytosol. PKCθ is a central molecule for TCR-mediated NF-κB activation. Phosphorylation of CARMA by PKCθ results in formation of stable CARMA/Bcl10/MALT1 complex and activation of IKK. Activated IKKβ kinase mediates phosphorylation of IκB molecules and recruitment of ubiquitin ligase. Activation of alternative NF-κB pathway is triggered by a subset of TNFR family members and is mediated by NIK and IKKα that phosphorylates p100. The ubiquitin-proteasome pathway is involved in activation of NF-κB via specific degradation of IκBs and processing of p100 to produce p52.
