I-TRAF is a novel TRAF-interacting protein that regulates TRAF-mediated signal transduction.
Tumor necrosis factor (TNF) receptor-associated factor (TRAF) proteins associate with and transduce signals from TNF receptor 2, CD40, and presumably other members of the TNF receptor superfamily. TRAF2 is required for CD40- and TNF-mediated activation of the transcription factor NF-kappa B. Here we describe the isolation and characterization of a novel TRAF-interacting protein, I-TRAF, that binds to the conserved TRAF-C domain of the three known TRAFs. Overexpression of I-TRAF inhibits TRAF2-mediated NF-kappa B activation signaled by CD40 and both TNF receptors. Thus, I-TRAF appears as a natural regulator of TRAF function that may act by maintaining TRAFs in a latent state.
Rothe
M
M
Tularik, Inc., South San Francisco, CA 94080, USA.
Xiong
J
J
Shu
H B
HB
Williamson
K
K
Goddard
A
A
Goeddel
D V
DV
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001426:Bacterial Proteins / Q000502:physiology*; D001665:Binding Sites; D002352:Carrier Proteins / Q000502:physiology*; D003001:Cloning, Molecular; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D047889:Receptors, Tumor Necrosis Factor, Type II; D015398:Signal Transduction; D047992:TNF Receptor-Associated Factor 2; D051636:X-Linked Inhibitor of Apoptosis Protein
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D001426:Bacterial Proteins; D002352:Carrier Proteins; D046911:Macromolecular Substances; D016328:NF-kappa B; D010455:Peptides; D011506:Proteins; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; C484406:TANK protein, human; D047992:TNF Receptor-Associated Factor 2; C100814:Tank protein, mouse; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human