Stephen M. Condon

TL;DR: It is shown that apoptosis caused by an IAC is blocked by the caspase 8 inhibitor crmA and that IAP antagonists activate NF-κB signaling via inhibtion of cIAP1.

TL;DR: It is shown that following LPS treatment, or LPS-induced necroptosis, the TLR adaptor protein TRIF and inhibitor of apoptosis proteins (IAPs: X-linked IAP, cellular IAP1 and IAP2) regulate RIPK3 and MLKL ubiquitylation, and RIPK 3 can promote NLRP3 inflammasome and IL-1β inflammatory responses independent ofMLKL and necroPTotic cell death.

TL;DR: It is shown that upon ligand binding, the TNF superfamily receptor FN14 recruits a cIAP1–Tnf receptor-associated factor 2 (TRAF2) complex that critically alters the balance of life/death signals emanating from TNF-R1 in immortalized cells.

TL;DR: The preclinical characterization of birinapant (TL32711) is reported, a bivalent SMAC-mimetic compound currently in clinical trials for the treatment of cancer, which supports the therapeutic combination of birInapant with multiple chemotherapies, in particular, those therapies that can induce TNF secretion.

TL;DR: It is shown that RING dimerization is essential for the E3 ligase activity of cI AP1 and cIAP2 because monomeric RING mutants could not interact with the ubiquitin-charged E2 enzyme and were resistant to Smac mimetic-induced autoubiquitylation.