TAK1‐binding protein 2 facilitates ubiquitination of TRAF6 and assembly of TRAF6 with IKK in the IL‐1 signaling pathway

Kishida, Satoshi; Sanjo, Hideki; Akira, Shizuo; Matsumoto, Kunihiro; Ninomiya‐Tsuji, Jun

doi:10.1111/j.1365-2443.2005.00852.x

Cited by 79 publications

(85 citation statements)

References 30 publications

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“…[18][19][20][21][22] TAK1 is recruited and activated through TAK1-binding protein 2 (TAB2) binding to the RIPK1 polyubiquitin chain. 23,24 Upon binding the polyubiquitin chain, TAK1 phosphorylates and activates the IKK complex composed of IKKa, IKKb and NEMO (also called IKKg), which leads to phosphorylation and degradation of IkB resulting in activation of NF-kB ( Figure 1). Activated TAK1 also phosphorylates and activates MAPKKs leading to activation of MAPKs such as ERK, p38 and JNK ( Figure 1).…”

Section: Tak1 Activation and Downstream Pathwaysmentioning

confidence: 99%

TAK1 control of cell death

2014

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Programmed cell death, a physiologic process for removing cells, is critically important in normal development and for elimination of damaged cells. Conversely, unattended cell death contributes to a variety of human disease pathogenesis. Thus, precise understanding of molecular mechanisms underlying control of cell death is important and relevant to public health. Recent studies emphasize that transforming growth factor-b-activated kinase 1 (TAK1) is a central regulator of cell death and is activated through a diverse set of intra-and extracellular stimuli. The physiologic importance of TAK1 and TAK1-binding proteins in cell survival and death has been demonstrated using a number of genetically engineered mice. These studies uncover an indispensable role of TAK1 and its binding proteins for maintenance of cell viability and tissue homeostasis in a variety of organs. TAK1 is known to control cell viability and inflammation through activating downstream effectors such as NF-jB and mitogen-activated protein kinases (MAPKs). It is also emerging that TAK1 regulates cell survival not solely through NF-jB but also through NF-jB-independent pathways such as oxidative stress and receptor-interacting protein kinase 1 (RIPK1) kinase activity-dependent pathway. Moreover, recent studies have identified TAK1's seemingly paradoxical role to induce programmed necrosis, also referred to as necroptosis. This review summarizes the consequences of TAK1 deficiency in different cell and tissue types from the perspective of cell death and also focuses on the mechanism by which TAK1 complex inhibits or promotes programmed cell death. This review serves to synthesize our current understanding of TAK1 in cell survival and death to identify promising directions for future research and TAK1's potential relevance to human disease pathogenesis.

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Section: Tak1 Activation and Downstream Pathwaysmentioning

confidence: 99%

TAK1 control of cell death

2014

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“…These contradictory results might be explained by the existence of TAK1-independent signaling pathways (see further) or possible effects of TAB1 on p65 transactivation. TAB2 and TAB3 contain two ubiquitin-binding domains that are required for their NF-kB activating function [49,57]: an N-terminal CUE domain and a C-terminal nuclear protein localization 4 zinc finger (NZF) [49,53].…”

Section: Il-1r and Tlr-4 Signaling To Nf-kbmentioning

confidence: 99%

“…Although the CUE domain interacts with ubiquitin in a yeast two-hybrid system, it is dispensable for TRAF6 binding [57]. The NZF domain, in contrast, is involved in binding to poly-ubiquitin chains of TRAF6 [49].…”

Section: Il-1r and Tlr-4 Signaling To Nf-kbmentioning

confidence: 99%

TLR-4, IL-1R and TNF-R signaling to NF-κB: variations on a common theme

Verstrepen

Bekaert

Chau

et al. 2008

Cell. Mol. Life Sci.

386

281

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Abstract. Toll-like receptors (TLRs) as well as the receptors for tumor necrosis factor (TNF-R) and interleukin-1 (IL-1R) play an important role in innate immunity by regulating the activity of distinct transcription factors such as nuclear factor-kB (NF-kB). TLR, IL-1R and TNF-R signaling to NF-kB converge on a common IkB kinase complex that phosphorylates the NF-kB inhibitory protein IkBa. However, upstream signaling components are in large part receptor-specific. Nevertheless, the principles of signaling are similar, involving the recruitment of specific adaptor proteins and the activation of kinase cascades in which protein-protein interactions are controlled by poly-ubiquitination. In this review, we will discuss our current knowledge of NF-kB signaling in response to TLR-4, TNF-R and IL-1R stimulation, with a special focus on the similarities and dissimilarities among these pathways.Keywords. Toll-like receptor 4, interleukin-1, tumor necrosis factor, NF-kB, signal transduction. NF-kB, does it still need to be introduced?Nuclear factor kB (NF-kB) is the generic name of a family of transcription factors that regulate the expression of a large number of genes involved in immune and inflammatory responses, as well as in cell survival, cell proliferation and cell differentiation. NFkB transcription factors are activated in response to various stimuli, including cytokines, infectious agents, injury and other stressful conditions requiring rapid reprogramming of gene expression. Inappropriate activation of the NF-kB signaling pathway is implicated in the pathogenesis of chronic inflammation and autoimmunity, certain hereditary disorders and various cancers. In mammals, the NF-kB family consists of five proteins sharing a highly conserved Rel homology domain: c-Rel, RelB, p65 (= RelA), p105 (= NF-kB1) and p100 (=NF-kB2). The first three contain Cterminal transactivation domains, while the others share a long C-terminal domain with multiple copies of ankyrin repeats, which inhibit their activation.

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“…The IRAK1-TRAF6 complex interacts with another membrane complex consisting of TAK1 and its pre-associated proteins, TAK1-binding protein (TAB)1, TAB2 and TAB3 [13,14], through the recognition of polyubiquitin chains on TRAF6 by highly conserved zinc finger domains in TAB2 and TAB3 [15] (Figure 2). Other reports indicate that TAB2 can interact with unmodified TRAF6 [16] and facilitate its ubiquitylation [17]. TAK1 and TAB2 are subsequently phosphorylated as part of the membrane complex and this is followed by translocation of a putative TRAF6-TAK1-TAB1-TAB2-TAB3 complex to the cytosol, at which TAK1 becomes activated by polyubiquitylated TRAF6 [10,13].…”

Section: The Importance Of Pellino Proteins For Tlr Signallingmentioning

confidence: 99%

“…The above-mentioned model favours the dissociation of the multi-molecular TRAF6-TAK1-TAB1-TAB2-TAB3 complex from IRAK1 at the membrane followed by its translocation to the cytosol, at which TAK1 becomes active, TAB2 promotes assembly of TRAF6 with the IKKs and TAK1 activates the IKKs [17]. Thus, IRAK1 remains at the membrane and the activation and assembly of TAK and the IKKs are spatially separate from IRAK1.…”

Section: Irak Polyubiquitylation and Tlr/il-1r Signallingmentioning

confidence: 99%