TAK1-TABs Complex: A Central Signalosome in Inflammatory Responses.

Yan-Ran Xu,Cao-Qi Lei

doi:10.3389/fimmu.2020.608976

Abstract

Transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) is a member of the MAPK kinase kinase (MAPKKK) family and has been implicated in the regulation of a wide range of physiological and pathological processes. TAK1 functions through assembling with its binding partners TAK1-binding proteins (TAB1, TAB2, and TAB3) and can be activated by a variety of stimuli such as tumor necrosis factor α (TNFα), interleukin-1β (IL-1β), and toll-like receptor ligands, and they play essential roles in the activation of NF-κB and MAPKs. Numerous studies have demonstrated that post-translational modifications play important roles in properly controlling the activity, stability, and assembly of TAK1-TABs complex according to the indicated cellular environment. This review focuses on the recent advances in TAK1-TABs-mediated signaling and the regulations of TAK1-TABs complex by post-translational modifications.

Highlights

The transcription factor nuclear factor kappa B (NF-kB) plays central roles in a variety of cellular events, such as immune and inflammatory responses, cell proliferation, autophagy, tissue remodeling, and metabolic regulation [1,2,3,4]
A series of knockout experiments proved that the Transforming growth factor-b-activated kinase 1 (TAK1)-TABs complex is essential for IL-1R, TNF receptor (TNFR), and Toll like receptors (TLRs)-mediated signaling pathways that lead to activation of MAPKs and NF
TAK1-TABs is associated with contact hypersensitivity [136] and neuronal death during cerebral ischemia [29]

Summary

Introduction

The transcription factor nuclear factor kappa B (NF-kB) plays central roles in a variety of cellular events, such as immune and inflammatory responses, cell proliferation, autophagy, tissue remodeling, and metabolic regulation [1,2,3,4]. TLR4-mediated activation of NFkB, p38, and JNK, and the production of proinflammatory cytokines are increased in TAK1-deficient neutrophils, suggesting a cell type-specific role for TAK1 in TLR signaling [32]. The TAK1-TABs complex has been widely studied, the roles of the individual binding proteins and the molecular mechanisms responsible for their activation in different cell types remains to be addressed.

Results

Conclusion