The TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral inhibitor of apoptosis proteins.
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 originally 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.
Rothe
M
M
Department of Molecular Biology Tularik, Incorporated, South San Francisco, California 94080, USA.
Pan
M G
MG
Henzel
W J
WJ
Ayres
T M
TM
Goeddel
D V
DV
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D018797:Cell Cycle Proteins / Q000502:physiology; D002460:Cell Line / Q000166:cytology / Q000502:physiology; D003001:Cloning, Molecular; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D007668:Kidney / Q000166:cytology / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011506:Proteins / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor / Q000302:isolation & purification / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000502:physiology; D047990:TNF Receptor-Associated Factor 1; D047992:TNF Receptor-Associated Factor 2; D044767:Ubiquitin-Protein Ligases; D014764:Viral Proteins / Q000502:physiology*
D018797:Cell Cycle Proteins; D051034:Inhibitor of Apoptosis Proteins; D011506:Proteins; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D047990:TNF Receptor-Associated Factor 1; D047992:TNF Receptor-Associated Factor 2; D014764:Viral Proteins; C086430:inhibitor of apoptosis, Nucleopolyhedrovirus; C494833:BIRC2 protein, human; C494834:Birc2 protein, mouse; D044767:Ubiquitin-Protein Ligases