Elsevier Inc. Ripk1 K63-ubiquitin M1-Ubiquitin Tradd M1-ubiquitination K63-ubiquitin ---- Tab3 K63-ubiquitin ---- Tab2 Cyld Casp8 ---- Fadd Fadd Casp8 --+> extrinsic apoptotic pathway extrinsic apoptotic pathway TRAF5 Traf2 Birc2 ---> Ripk1 Birc3 ---- Traf2 Birc3 Ripk1 --+> Map3k7 Birc3 ---- LUBAC complex Bag4 Fadd ---- Tradd Tnfrsf1a ---- Tradd Tnfrsf1a Adam17 ---> Tnf Tnf ---- Tnfrsf1a Tnf Bag4 ---| Tnfrsf1a Tradd ---- TRAF5 Tradd ---- Traf2 Ripk1 ---- Tradd Birc2 Birc2 ---- LUBAC complex LUBAC complex ---- TRAF5 LUBAC complex ---- Tradd LUBAC complex ---- Traf2 A20 ubiquitin-editing complex ---| K63-polyubiquitination Adam17 nuclear factor kappa B signaling pathway Map3k7 --+> nuclear factor kappa B signaling pathway p38 MAPK signaling pathway Map3k7 Map3k7 ---- Tab1 LUBAC complex ---> Ripk1 Birc3 ---> Ripk1 Map3k7 --+> p38 MAPK signaling pathway c-Jun N-terminal kinases MAPK signaling pathway Map3k7 --+> c-Jun N-terminal kinases MAPK signaling pathway Tab1 Tab2 Tab3 Casp8 Map3k7 ---- Tab3 Map3k7 ---- Tab2 A20 ubiquitin-editing complex LUBAC complex K63-polyubiquitination Cyld ---| Map3k7 Cyld ---| K63-polyubiquitination