I-TRAF is a novel TRAF-interacting protein that regulates TRAF-mediated signal transduction

Tularik, Inc., South San Francisco, CA 94080, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 09/1996; 93(16):8241-6. DOI: 10.1073/pnas.93.16.8241
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ABSTRACT 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.

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Available from: Dave Goeddel, Aug 27, 2015
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    • "TANK (also known as I-TRAF) was first identified by two groups working independently to find binding partners of TNF-receptor associated factor (TRAF) family proteins. Cheng and Baltimore showed that TANK was a net activator of TRAF2- mediated NF-kappa B activation whereas Rothe et al. found that TANK inhibited TRAF2- dependent signaling (Cheng and Baltimore, 1996; Rothe et al., 1996). TANK has also been found to be a potent suppressor of Toll-like receptor (TLR)-mediated induction of proinflammatory cytokines (Kawagoe et al., 2009). "
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    • "Xenopus Tlrs5 protein is a paralog of TLR5 because a Xenopus ortholog of TLR5 has been registered in the NCBI database (NCBI Accession Number: NP_001088449), and both tlrs5 and tlr5 genes have been distinctly identified in fish (Tsujita et al. 2004; Baoprasertkul et al. 2007). In mammals, TANK (also called I- TRAF) protein has been identified as an adaptor molecule for TRAF-mediated NF-jB activation (Cheng & Baltimore 1996; Rothe et al. 1996). The Xenopus Tank showed 29% identity and 45% similarity to human TANK at amino acid sequence level (Fig. S3B in Supporting Information). "
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    • "However, there are few reports that cell cycle regulators also regulate the activity of NF-␬B. For example, the adaptor protein TANK regulates TRAF2-induced NF-␬B signaling pathway was reported (Cheng and Baltimore, 1996; Rothe et al., 1996). Recently it was been revealed that the TANK binds to downstream IKKs complex and regulates its activation (Chariot et al., 2002; Bonif et al., 2006). "
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