OTUD7D (Cezanne) negatively regulates the non-canonical NFkappaB pathway by removing Lys-48-linked polyubiquitin chains from TRAF6, preventing TRAF6 proteolysis, which causes over-activation of non-canonical NFkappaB and negative regulation of B-cell responses (Evans et al. 2001).

TNFAIP3 has the opposite effect, it can remove K63-linked ubiquitin from TRAF6, which terminates signalling by Toll-like receptors (Boone et al. 2004). TNFAIP3 is essential for the termination of NFkappaB activation in response to multiple stimuli such as IL-1beta, TNF, IL-6, CD40 and lipopolysaccharide (LPS) (Vereecke et al. 2009).