TAK1 kinase switches cell fate from apoptosis to necrosis following TNF stimulation

Morioka, Sho; Broglie, Peter M.; Omori, Emily; Ikeda, Yuka; Takaesu, Giichi; Matsumoto, Kunihiro; Ninomiya‐Tsuji, Jun

doi:10.1083/jcb.201305070

Cited by 84 publications

(113 citation statements)

References 60 publications

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“…The other is that additional deletion of Tak1 in Tab2-deficient fibroblasts solely induces caspasedependent apoptosis following TNFa stimulation. 49 These results collectively reveal an unexpected role of TAK1 in cell death pathways, as an inducer of necroptosis ( Figure 3). Furthermore, it has been shown that TAK1 activates RIPK3, reciprocally RIPK3 activates TAK1, and these activations are facilitated by RIPK1, which mediates TAK1-RIPK1-RIPK3 binding.…”

Section: Tak1 As a Necroptosis Inducermentioning

confidence: 72%

“…[46][47][48] Inhibition of TAK1 is usually followed by caspase-8 and -3 activation in response to TNFa, which suggests that TAK1 inhibits caspase activation cascade to block apoptotic cell death. 49 Thus, TAK1 is likely to blunt the formation or activation of Complex IIa. Recent studies revealed two major mechanisms through which TAK1 inhibits caspase activation ( Figure 2).…”

Section: Tak1 Inhibits Apoptosismentioning

confidence: 99%

“…TAK1-ROS-cIAP pathway: TNFa-induced caspase activation and subsequent cell death in Tak1-deficient cells is effectively blocked by gene deletion of Ripk1 or necrostatin-1, a pharmacologic inhibitor of RIPK1 kinase activity. 49,58,59 Thus, Tak1 deficiency engages RIPK1-dependent apoptosis.…”

Section: Tak1 Control Of Cell Death Sr Mihaly Et Almentioning

confidence: 99%

“…38 Despite the presence of TAK1 activation, Tab2-deficient fibroblasts are killed by TNFa challenge. 49 Interestingly, while Tak1 deficiency induces caspase activation leading to apoptosis upon TNFa stimulation, Tab2 deficiency shows almost no caspase activation and results in cell death having typical necrotic features such as plasma membrane rupture. 49 Furthermore, TNFa-induced cell death in Tab2-deficient fibroblasts is almost completely rescued by Ripk3 deletion, whereas Ripk3 deletion has no effect on Tak1-deficient fibroblasts.…”

Section: Tak1 As a Necroptosis Inducermentioning

confidence: 99%

“…Furthermore, it has been shown that TAK1 activates RIPK3, reciprocally RIPK3 activates TAK1, and these activations are facilitated by RIPK1, which mediates TAK1-RIPK1-RIPK3 binding. 49 Thus, TAK1-RIPK1-RIPK3 is activated by a positive feedforward mechanism ( Figure 3). 49 How is TAK-RIPK1-RIPK3 assembled?…”

Section: Tak1 As a Necroptosis Inducermentioning

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: Tak1 As a Necroptosis Inducermentioning

confidence: 72%

Section: Tak1 Inhibits Apoptosismentioning

confidence: 99%

Section: Tak1 Control Of Cell Death Sr Mihaly Et Almentioning

confidence: 99%

Section: Tak1 As a Necroptosis Inducermentioning

confidence: 99%

Section: Tak1 As a Necroptosis Inducermentioning

confidence: 99%

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TAK1 control of cell death

2014

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TAK1 Phosphorylates RASSF9 and Inhibits Esophageal Squamous Tumor Cell Proliferation by Targeting the RAS/MEK/ERK Axis

Shi

Mao

et al. 2021

Advanced Science

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TGF‐β‐activated kinase 1 (TAK1), a serine/threonine kinase, is a key intermediate in several signaling pathways. However, its role in tumorigenesis is still not understood well. In this study, it is found that TAK1 expression decreases in esophageal tumor tissues and cell lines. In vitro experiments demonstrate that proliferation of esophageal tumor cells is enhanced by knockdown of TAK1 expression and attenuated by elevated expression of TAK1. Using a subcutaneous tumor model, these observations are confirmed in vivo. Based on the results from co‐immunoprecipitation coupled with mass spectrometry, Ras association domain family 9 (RASSF9) is identified as a downstream target of TAK1. TAK1 phosphorylates RASSF9 at S284, which leads to reduced RAS dimerization, thereby blocking RAF/MEK/ERK signal transduction. Clinical survey reveals that TAK1 expression is inversely correlated with survival in esophageal cancer patients. Taken together, the data reveal that TAK1‐mediated phosphorylation of RASSF9 at Ser284 negatively regulates esophageal tumor cell proliferation via inhibition of the RAS/MEK/ERK axis.

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Tak1

Morioka¹

2016

Encyclopedia of Signaling Molecules

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TAK1 kinase switches cell fate from apoptosis to necrosis following TNF stimulation

Abstract: Activation of the TAK1 kinase drives RIPK3-dependent necrosis and inhibits apoptosis downstream of TNF-α stimulation.

Cited by 84 publications

References 60 publications

TAK1 control of cell death

TAK1 control of cell death

TAK1 Phosphorylates RASSF9 and Inhibits Esophageal Squamous Tumor Cell Proliferation by Targeting the RAS/MEK/ERK Axis

Tak1

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