TAB2 and TAB3 Activate the NF-κB Pathway through Binding to Polyubiquitin Chains

Kanayama, Atsuhiro; Seth, Rashu B.; Sun, Lijun; Kwee, Chee; Hong, Mei; Shaito, Abdullah; Chiu, Yu Hsin; Deng, Li; Chen, Zhijian J.

doi:10.1016/j.molcel.2004.08.008

Cited by 799 publications

(736 citation statements)

References 54 publications

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“…TAB2 and TAB3 each have Np14 zinc-finger domain, which is necessary for recruitment of TAK1 to the RIPK1 polyubiquitin chain in the TNFa signaling pathway ( Figure 1). 18,24 Consistently, inhibition of TAB2 reduces TAK1 activity in several tissues and cell types. 32,36,37 However, Broglie et al 38 described that loss of Tab2 in dermal fibroblasts rather prolonged and increased the activation of TAK1 following TNFa stimulation.…”

Section: The Roles Of Tak1-binding Proteins In Tak1 Activationmentioning

confidence: 78%

“…[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%

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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: The Roles Of Tak1-binding Proteins In Tak1 Activationmentioning

confidence: 78%

Section: Tak1 Activation and Downstream Pathwaysmentioning

confidence: 99%

TAK1 control of cell death

2014

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“…In this process, TRAF6 interacts with the E2 ubiquitin-conjugating heterodimer UbcH13-Uev1a, resulting in covalent attachment of Lys63-linked polyubiquitin chains to TRAF6 [12]. 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].…”

Section: The Importance Of Pellino Proteins For Tlr Signallingmentioning

confidence: 99%

The Pellino family: IRAK E3 ligases with emerging roles in innate immune signalling

Moynagh

2009

Trends in Immunology

132

102

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“…5,[10][11][12][13] Ultimately, activation of IKKβ leads to the phosphorylation and proteasomal degradation of IκBα and the nuclear translocation of NF-κB, a pathway defined as the classical, or the canonical, NF-κB pathway. [14][15][16] Besides its role in the activation of NF-κB, the dissociation of complex I from TNFR1 triggers the recruitment of Fas-associated protein with death domain (FADD) and caspase-8 to form a cytosolic death complex, initially defined as complex II. 3 TNFR1 induces apoptosis through two distinct caspase-8 activation pathways.…”

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confidence: 99%

NIK promotes tissue destruction independently of the alternative NF-κB pathway through TNFR1/RIP1-induced apoptosis

et al. 2015

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NF-κB-inducing kinase (NIK) is well-known for its role in promoting p100/NF-κB2 processing into p52, a process defined as the alternative, or non-canonical, NF-κB pathway. Here we reveal an unexpected new role of NIK in TNFR1-mediated RIP1-dependent apoptosis, a consequence of TNFR1 activation observed in c-IAP1/2-depleted conditions. We show that NIK stabilization, obtained by activation of the non-death TNFRs Fn14 or LTβR, is required for TNFα-mediated apoptosis. These apoptotic stimuli trigger the depletion of c-IAP1/2, the phosphorylation of RIP1 and the RIP1 kinase-dependent assembly of the RIP1/FADD/caspase-8 complex.In the absence of NIK, the phosphorylation of RIP1 and the formation of RIP1/FADD/caspase-8 complex are compromised while c-IAP1/2 depletion is unaffected. In vitro kinase assays revealed that recombinant RIP1 is a bona fide substrate of NIK. In vivo, we demonstrated the requirement of NIK pro-death function, but not the processing of its substrate p100 into p52, in a mouse model of TNFR1/LTβR-induced thymus involution. In addition, we also highlight a role for NIK in hepatocyte apoptosis in a mouse model of virus-induced TNFR1/RIP1-dependent liver damage. We conclude that NIK not only contributes to lymphoid organogenesis, inflammation and cell survival but also to TNFR1/RIP1-dependent cell death independently of the alternative NF-κB pathway.

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TAB2 and TAB3 Activate the NF-κB Pathway through Binding to Polyubiquitin Chains

Cited by 799 publications

References 54 publications

TAK1 control of cell death

TAK1 control of cell death

The Pellino family: IRAK E3 ligases with emerging roles in innate immune signalling

NIK promotes tissue destruction independently of the alternative NF-κB pathway through TNFR1/RIP1-induced apoptosis

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