E3 Ubiquitin ligase ZNRF4 negatively regulates NOD2 signalling and induces tolerance to MDP

Prolonged NOD2 ligand engagement induces tolerance and attenuated NOD2 signalling, but the molecular mechanisms leading to this tolerance induction are unclear. Here the authors show that the degradation of a NOD2 adaptor, RIP2, by the E3 ligase ZNRF4 is essential for the down-regulation of NOD2 signalling.