Fig. 8. Schematic representation of TNF signaling by OTUD7b in DCs.

OTUD7b cleaves K48-linked polyubiquitin chains from TRAF2 and prevents its proteasomal degradation. The stabilized TRAF2 facilitates K63-linked polyubiquitination of RIPK1, which mediates (i) activation of NF-κB and MAP kinases pathway leading to the expression of anti-apoptotic molecules cFLIP and Bcl-xL. cFLIP and Bcl-xL serve as late checkpoint inhibitors of RIPK1-independent apoptosis (ii) K63-linked polyubiquitination of RIPK1 prevents its autophosphorylation at S166 and formation of the death inducing cytosolic complex II comprising of RIPK1, procaspase-8, and FADD which serves as an early checkpoint for the inhibition of RIPK1-mediated apoptosis.