Post-translational modifications regulate distinct functions of CARMA1 and BCL10

Activation of the transcription factor nuclear factor (NF)-κB is essential for the normal functioning of the immune system. Deregulated NF-κB signalling in lymphocytes can lead to immunodeficiency, but also to autoimmunity or lymphomas. Many of the signalling components controlling NF-κB activation in lymphocytes are now known, but it is less clear how distinct molecular components of this pathway are regulated. Here, we summarize recent findings on post-translational modifications of intracellular components of this pathway. Phosphorylation of the CARMA1 and BCL10 proteins and ubiquitylation of BCL10 affect the formation and stability of the CARMA1–BCL10–MALT1 (CBM) complex, and also control negative feedback regulation of the NF-κB signalling pathway. Moreover, the study of BCL10 phosphorylation isoforms has revealed a new mechanism controlling BCL10 nuclear translocation and an unexpected role for BCL10 in the regulation of the actin cytoskeleton.