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TIRAP in the mechanism of inflammation

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Title: TIRAP in the mechanism of inflammation
Authors: Thurston, T
Rajpoot, S
Wary, K
Ibbott, R
Liu, D
Saqib, U
Baig, M
Item Type: Journal Article
Abstract: The Toll-interleukin-1 Receptor (TIR) domain-containing adaptor protein (TIRAP) represents a key intracellular signalling molecule regulating diverse immune responses. Its capacity to function as an adaptor molecule has been widely investigated in relation to Toll-like Receptor (TLR)-mediated innate immune signalling. Since the discovery of TIRAP in 2001, initial studies were mainly focused on its role as an adaptor protein that couples Myeloid differentiation factor 88 (MyD88) with TLRs, to activate MyD88-dependent TLRs signalling. Subsequent studies delineated TIRAP’s role as a transducer of signalling events through its interaction with non-TLR signalling mediators. Indeed, the ability of TIRAP to interact with an array of intracellular signalling mediators suggests its central role in various immune responses. Therefore, continued studies that elucidate the molecular basis of various TIRAP-protein interactions and how they affect the signalling magnitude, should provide key information on the inflammatory disease mechanisms. This review summarizes the TIRAP recruitment to activated receptors and discusses the mechanism of interactions in relation to the signalling that precede acute and chronic inflammatory diseases. Furthermore, we highlighted the significance of TIRAP-TIR domain containing binding sites for several intracellular inflammatory signalling molecules. Collectively, we discuss the importance of the TIR domain in TIRAP as a key interface involved in protein interactions which could hence serve as a therapeutic target to dampen the extent of acute and chronic inflammatory conditions.
Issue Date: Jul-2021
Date of Acceptance: 23-Jun-2021
URI: http://hdl.handle.net/10044/1/90626
DOI: 10.3389/fimmu.2021.697588
ISSN: 1664-3224
Publisher: Frontiers Media
Start Page: 1
End Page: 12
Journal / Book Title: Frontiers in Immunology
Volume: 12
Copyright Statement: © 2021 Rajpoot, Wary, Ibbott, Liu, Saqib, Thurston and Baig. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Sponsor/Funder: Biotechnology and Biological Sciences Research Council (BBSRC)
Funder's Grant Number: BB/R011834/1
Keywords: TIRAP (TIR domain-containing adaptor protein)
TLR signaling
inflammatory disease
protein-protein interaction (PPI)
1107 Immunology
1108 Medical Microbiology
Publication Status: Published
Article Number: 697588
Online Publication Date: 2021-07-08
Appears in Collections:Department of Infectious Diseases

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