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Int. J. Mol. Sci. 2018, 19(8), 2457; https://doi.org/10.3390/ijms19082457

In Vitro Inhibitory Mechanism Effect of TRAIP on the Function of TRAF2 Revealed by Characterization of Interaction Domains

1
Department of Chemistry and Biochemistry, School of Natural Science and Graduate School of Biochemistry at Yeungnam University, Gyeongsan 38541, Korea
2
College of Pharmacy, Chung-Ang University, Seoul 06974, Korea
3
New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 41061, Korea
4
R&D Center, Polus, Inc., 32 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Korea
*
Author to whom correspondence should be addressed.
Received: 30 July 2018 / Revised: 17 August 2018 / Accepted: 17 August 2018 / Published: 20 August 2018
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

TRAF-interacting protein (TRAIP), a negative regulator of TNF-induced-nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation, inhibits adaptor protein TRAF2 by direct interaction and is critical in apoptosis, cell proliferation, antiviral response, and embryonic development. Although the critical function of TRAIP in NF-κB signaling is well-known, the molecular inhibitory mechanism of TRAIP remains unclear. We found that the TRAIP coiled-coil domain altered its stoichiometry between dimer and trimer in a concentration-dependent manner. Additionally, the TRAIP RING domain induced even higher-ordered assembly, which was necessary for interacting with the TRAF-N domain of TRAF2 but not TRAF1. Characterization of the TRAF-N domains of TRAF1 and TRAF2, the tentative TRAIP-binding region of TRAFs, suggested the molecular basis of the inhibitory effect of TRAIP on TRAF2 in NF-κB signaling. View Full-Text
Keywords: immune response; nuclear factor-κB; tumor necrosis factor-receptor associated factor; TRAF-interacting protein; protein interaction immune response; nuclear factor-κB; tumor necrosis factor-receptor associated factor; TRAF-interacting protein; protein interaction
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Bhat, E.A.; Kim, C.M.; Kim, S.; Park, H.H. In Vitro Inhibitory Mechanism Effect of TRAIP on the Function of TRAF2 Revealed by Characterization of Interaction Domains. Int. J. Mol. Sci. 2018, 19, 2457.

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