The TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral inhibitor of apoptosis proteins

• Published in: Cell Vol. 83; no. 7; pp. 1243 - 1252
• Main Authors: Rothe, Mike, Pan, Ming-Gui, Henzel, William J., Ayres, T.Merrill, V. Goeddel, David
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 29.12.1995
• Subjects: Animals; Apoptosis - physiology; baculovirus; Cell Cycle Proteins - physiology; Cell Line - cytology; Cell Line - physiology; Cloning, Molecular; Humans; Inhibitor of Apoptosis Proteins; Kidney - cytology; Kidney - physiology; Mice; Molecular Sequence Data; Molecular Weight; Proteins - physiology; Receptors, Tumor Necrosis Factor - isolation & purification; Receptors, Tumor Necrosis Factor - physiology; RNA, Messenger - analysis; Sequence Homology, Amino Acid; Signal Transduction - physiology; T-Lymphocytes, Cytotoxic - cytology; T-Lymphocytes, Cytotoxic - physiology; TNF Receptor-Associated Factor 1; TNF Receptor-Associated Factor 2; Ubiquitin-Protein Ligases; Viral Proteins - physiology
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/0092-8674(95)90149-3

The 75 kDa tumor necrosis factor receptor (TNFR2) transduces extracellular signals via receptor-associated cytoplasmic proteins. Two of these signal transducers, TRAF1 and TRAF2, were isolated and characterized previously. We report here the biochemical purification and subsequent molecular cloning of two novel TNFR2-associated proteins, designated c-IAP1 and c-IAP2, that are closely related mammalian members of the inhibitor of apoptosis protein (IAP) family orginally identified in baculoviruses. The viral and cellular IAPs contain N-terminal baculovirus IAP repeat (BIR) motifs and a C-terminal RING finger. The c-IAPs do not directly contact TNFR2, but rather associate with TRAF1 and TRAF2 through their N-terminal BIR motif-comprising domain. The recruitment of c-IAP1 or c-IAP2 to the TNFR2 signaling complex requires a TRAF2-TRAF1 heterocomplex.