The classical pathway for activation of NF-kB, a key transcriptional regulator of the immune system, is controlled by the IKK complex.  Activated IKK phosphorylates IkB which is ubiquitinated and rapidly degraded, allowing NF-kB to translocate from the cytoplasm to the nucleus where it activates gene transcription. However, the mechanisms regarding IKK activation have been elusive.

Now CARMA1, Bcl-10, and MALT1 are helping to fill in the blanks of IKK activation. These proteins are downstream of the T cell receptor (TCR) and upstream of the IKK complex (Fig. 1). Antigen-TCR signaling in the adaptive immune system leads to PKC-q activation and formation of an oligomerization-ubiquitination (Ub)-phosphorylation (P) pathway leading to activated IKK. Oligomerization-Ub-P pathways have also been found to mediate