TAK1, but not TAB1 or TAB2, plays an essential role in multiple signaling pathways in vivo

Shim, Jae-Hyuck; Xiao, Changchun; Paschal, Amber; Bailey, Scott; Rao, P. Nagesh; Hayden, Matthew S.; Lee, Ki-Young; Bussey, Crystal; Steckel, Michael; Tanaka, Nobuyuki; Yamada, Gen; Akira, Shizuo; Matsumoto, Kunihiro; Ghosh, Sankar

doi:10.1101/gad.1360605

Cited by 648 publications

(665 citation statements)

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“…The link between TRAF6 and the IKK complex remains somewhat enigmatic, although a few key players are known. The kinase TAK1 (TGFb-activated kinase-1) is required for NF-kB, as well as AP-1 and extracellular signalrelated kinase (ERK), activation downstream of MyD88 Shim et al, 2005). Although it is widely accepted that ubiquitination is a key switch at this crucial step of NF-kB activation, considerable work at the molecular level remains to be done to understand how ubiquitination leads to activation.…”

Section: Toll-like Receptorsmentioning

confidence: 99%

“…Upon ubiquitination, RIP1 can bind directly to NEMO and recruit IKK independent of TRAF2 (Zhang et al, 2000). Signaling downstream of RIP1 requires TAK1 for the activation of IKK Shim et al, 2005). Whether TAK1 directly activates IKK or this process proceeds through an intermediary such as MEKK3 is not yet clear (Takaesu et al, 2003;Li et al, 2006).…”

Section: Tnf-r Superfamily Signalingmentioning

confidence: 99%

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NF-κB and the immune response

2006

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Section: Toll-like Receptorsmentioning

confidence: 99%

Section: Tnf-r Superfamily Signalingmentioning

confidence: 99%

NF-κB and the immune response

2006

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“…Activated TAK1 also phosphorylates and activates MAPKKs leading to activation of MAPKs such as ERK, p38 and JNK ( Figure 1). 6,25 NF-kB and MAPKs induce downstream expression of inflammatory cytokines and antiapoptotic proteins such as cellular FLICE-like inhibitory protein (c-FLIP) and cIAPs. 26,27 Drawing a link between TAK1 signaling and metabolism, studies have found that starvation and TRAIL induce autophagy in which TAK1 is actively involved by activating AMP-activated protein kinase and IKKs.…”

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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“…Two main NF-kB-activating signalling pathways have been characterized and referred to as the 'classical' or 'canonical' pathway and the 'alternative' or 'non-canonical' pathway (Bonizzi and Karin, 2004). The classical pathway, which is triggered by cytokines such as tumor necrosis factor-a (TNFa), interleukin (IL)-1b, or by the ligand for the T-cell or B-cell receptor, leads to IkBa degradation and subsequent nuclear import of the p50/p65 heterodimer through a NEMO/IKKg-dependent pathway (Li and Verma, 2002;Shim et al, 2005). The alternative pathway, which is triggered by cytokines such as lymphotoxin-b (LTb), BAFF and CD40, relies on the NIK-and IKKa-mediated phosphorylation and processing of the inhibitory protein p100 into p52.…”

Section: Introductionmentioning

confidence: 99%

Matrix Metalloproteinase-9 gene induction by a truncated oncogenic NF-κB2 protein involves the recruitment of MLL1 and MLL2 H3K4 histone methyltransferase complexes

et al. 2009

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Constitutive nuclear factor (NF)-jB activation in haematological malignancies is caused in several cases by loss of function mutations within the coding sequence of NF-jB inhibitory molecules such as IjBa or p100. Hut-78, a truncated form of p100, constitutively generates p52 and contributes to the development of T-cell lymphomas but the molecular mechanism underlying this oncogenic potential remains unclear. We show here that MMP9 gene expression is induced through the alternative NF-jB-activating pathway in fibroblasts and also on Hut-78 or p52 overexpression in fibroblasts as well as in lymphoma cells. p52 is critical for Hut-78-mediated MMP9 gene induction as a Hut-78 mutant as well as other truncated NF-jB2 proteins that are not processed into p52 failed to induce the expression of this metalloproteinase. Conversely, MMP9 gene expression is impaired in p52-depleted HUT-78 cells. Interestingly, MLL1 and MLL2 H3K4 methyltransferase complexes are tethered by p52 on the MMP9 but not on the IjBa promoter, and the H3K4 trimethyltransferase activity recruited on the MMP9 promoter is impaired in p52-depleted HUT-78 cells. Moreover, MLL1 and MLL2 are associated with Hut-78 in a native chromatin-enriched extract. Thus, we identified a molecular mechanism by which the recruitment of a H3K4 histone methyltransferase complex on the promoter of a NF-jB-dependent gene induces its expression and potentially the invasive potential of lymphoma cells harbouring constitutive activity of the alternative NF-jB-activating pathway.

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TAK1, but not TAB1 or TAB2, plays an essential role in multiple signaling pathways in vivo

Abstract: TGF-␤-activated kinase 1 (TAK1),[Keywords: JNK; NF-B; TAB1; TAB2; TAK1; TGF-␤] Supplemental material is available at http://www.genesdev.org.

Cited by 648 publications

References 50 publications

NF-κB and the immune response

NF-κB and the immune response

TAK1 control of cell death

Matrix Metalloproteinase-9 gene induction by a truncated oncogenic NF-κB2 protein involves the recruitment of MLL1 and MLL2 H3K4 histone methyltransferase complexes

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