A20 is a negative regulator of BCL10- and CARMA3-mediated activation of NF-κB

Abstract

The molecular complex containing CARMA proteins, BCL10 and TRAF6 has been identified recently as a key component in the signal transduction pathways that regulate activation of the nuclear factor KB (NF-KB) transcription factor. Here, we report that the inducible protein A20 negatively regulates these signaling cascades by means of its deubiquitylation activity. We show that A20 perturbs assembly of the cognplex containing CARMA3, BCL10 and IKKγ/NEMO, thereby suppressing activation of NF-KB. Together, our results further define the molecular mechanisms that control activation of NF-KB and reveal a function for A20 in the regulation of CARMA and BCL10 activity in lymphoid and non-lymphoid cells.