TAK1 control of cell death

Mihaly, September R.; Ninomiya‐Tsuji, Jun; Morioka, Sho

doi:10.1038/cdd.2014.123

Cited by 229 publications

(280 citation statements)

References 133 publications

(212 reference statements)

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“…The kinase activity of RIPK1 has also been known to mediate TNFα-mediated apoptosis, termed RDA, when cells are deficient for TAK1, IKKs, or cIAP1/2 (Mihaly et al 2014;Dondelinger et al 2015). Spata2 −/− MEFs showed a partial resistance against RDA induced by the TNFα and TAK1 inhibitor (5Z)-7-oxozeaenol (5Z-7) compared with Spata2 + MEFs (Fig.…”

Section: Spata2 Regulates Apoptosismentioning

confidence: 99%

SPATA2 regulates the activation of RIPK1 by modulating linear ubiquitination

Wei

Liu

et al. 2017

Genes Dev.

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Stimulation of cells with TNFα leads to the formation of the TNF-R1 signaling complex (TNF-RSC) to mediate downstream cellular fate decision. Activation of the TNF-RSC is modulated by different types of ubiquitination and may lead to cell death, including apoptosis and necroptosis, in both RIPK1-dependent and RIPK1-independent manners. Spata2 (spermatogenesis-associated 2) is an adaptor protein recruited into the TNF-RSC to modulate the interaction between the linear ubiquitin chain assembly complex (LUBAC) and the deubiquitinase CYLD (cylindromatosis). However, the mechanism by which Spata2 regulates the activation of RIPK1 is unclear. Here, we report that Spata2-deficient cells show resistance to RIPK1-dependent apoptosis and necroptosis and are also partially protected against RIPK1-independent apoptosis. Spata2 deficiency promotes M1 ubiquitination of RIPK1 to inhibit RIPK1 kinase activity. Furthermore, we provide biochemical evidence for the USP domain of CYLD and the PUB domain of the SPATA2 complex preferentially deubiquitinating the M1 ubiquitin chain in vitro. Spata2 deficiency also promotes the activation of MKK4 and JNK and cytokine production independently of RIPK1 kinase activity. Spata2 deficiency sensitizes mice to systemic inflammatory response syndrome (SIRS) induced by TNFα, which can be suppressed by RIPK1 inhibitor Nec-1s. Thus, Spata2 can regulate inflammatory response and cell death in both RIPK1-dependent and RIPK1-independent manners.

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Section: Spata2 Regulates Apoptosismentioning

confidence: 99%

SPATA2 regulates the activation of RIPK1 by modulating linear ubiquitination

Wei

Liu

et al. 2017

Genes Dev.

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“…The biological effects of TAK1 are involved in almost all aspects of cell function, including cell proliferation, differentiation, survival, apoptosis, autophagy and the inflammatory immune response 27. Increasing evidence has manifested that TAK1 is widely expressed in multiple important organs and is involved in the pathophysiological processes of acute injury by regulating and mediating multiple signalling pathways7, 28 In our previous study, we demonstrated that TAK1 mediated apoptosis in ischaemia‐reperfusion of the kidney 29.…”

Section: Discussionmentioning

confidence: 96%

TAK1 mediates excessive autophagy via p38 and ERK in cisplatin‐induced acute kidney injury

Zhou

Fan

Zhong

et al. 2018

J Cellular Molecular Medi

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The ability of cisplatin (cis‐diamminedichloroplatinum II) toxicity to induce acute kidney injury (AKI) has attracted people's attention and concern for a long time, but its molecular mechanisms are still widely unknown. We found that the expression of transforming growth factor‐β (TGF‐β)‐activated kinase 1 (TAK1) could be increased in kidneys of mice administrated with cisplatin. Autophagy is an evolutionarily conserved catabolic pathway and is involved in various acute and chronic injuries. Moreover, p38 MAPK (mitogen‐activated protein kinase) and ERK regulate autophagy in response to various stimuli. Therefore, our hypothesis is that cisplatin activates TAK1, which phosphorylates p38 and ERK, leading to excessive autophagy of tubular epithelial cells and thus exacerbating kidney damage. Here, BALB/c mice were intraperitoneally injected with a TAK1 inhibitor and were then administrated with sham or cisplatin at 20 mg/kg by intraperitoneal injection. Compared with mice in the vehicle cisplatin group, mice intraperitoneally injected with a TAK1 inhibitor were found to have lower serum creatinine and less tubular damage following cisplatin‐induced AKI. Furthermore, inhibition of TAK1 reduced p38 and Erk phosphorylation, decreased expression of LC3II and reversed the down‐regulation of P62 expression induced by cisplatin. The hypothesis was verified with tubular epithelial cells administrated with cisplatin in vitro. Finally, p38 inhibitor or ERK inhibitor abated autophagy activation and cell viability reduction in tubular epithelial cells treated with cisplatin plus TAK1 overexpression vector. Taken together, our results show that cisplatin activates TAK1, which phosphorylates p38 and ERK, leading to excessive autophagy of tubular epithelial cells that exacerbates kidney damage.

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“…Activated TAK1 can activate RIPK3-MLKL axis independently of RIPK1 leading to regulated necrotic cell death. 36 Interestingly, Nec-1s treatment results in a slight but significant enhancement of survival of RIPK1 K45A macrophages following LPS, TNFα or IFNβ treatment ( Figure 1a). As Nec-1s, in contrast to Nec-1, specifically inhibits the kinase activity of RIPK1, 21 these results suggest that Nec-1s may inactivate other regions of RIPK1, which may impact necroptosis further.…”

Section: Ripk1 Interacts With Various Proteins Such As Ciaps Andmentioning

confidence: 94%

K45A mutation of RIPK1 results in poor necroptosis and cytokine signaling in macrophages, which impacts inflammatory responses in vivo

et al. 2016

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Receptor interacting protein kinase 1 (RIPK1) participates in several cell signaling complexes that promote cell activation and cell death. Stimulation of RIPK1 in the absence of caspase signaling induces regulated necrosis (necroptosis), which promotes an inflammatory response. Understanding of the mechanisms through which RIPK1 promotes inflammation has been unclear. Herein we have evaluated the impact of a K45A mutation of RIPK1 on necroptosis of macrophages and the activation of inflammatory response. We show that K45A mutation of RIPK1 results in attenuated necroptosis of macrophages in response to stimulation with LPS, TNFα and IFNβ in the absence of caspase signaling. Impairment in necroptosis correlated with poor phosphorylation of RIPK1, RIPK3 and reduced trimerization of MLKL. Furthermore, K45A mutation of RIPK1 resulted in poor STAT1 phosphorylation (at S727) and expression of RANTES and MIP-1α following TNF-R engagement in the absence of caspase activation. Our results further indicate that in the absence of stimulation by pathogen-associated molecular patterns (PAMPs), cellular inhibitors of apoptotic proteins (cIAPs) prevent the K45-dependent auto-phosphorylation of RIPK1, leading to resistance against necroptosis. Finally, RIPK1K45A mice displayed attenuated inflammatory response in vivo as they were significantly resistant against endotoxin shock, but highly susceptible against a challenge with Salmonella typhimurium. This correlated with reduced expression of IL-1β and ROS, and poor processing of caspase 8 by RIPK1K45A macrophages. Overall, these results indicate that K45 mediated kinase activity of RIPK1 is not only important for necroptosis but it also has a key role in promoting cytokine signaling and host response to inflammatory stimuli. Apoptosis is considered as the predominant, programmed pathway of cell death; however, recently several pathways of regulated cell death have been shown to operate in cells that are considered highly inflammatory.1,2 Although apoptosis has a major role during fetal development, 3 regulated necrotic cell death does not appear to influence fetal development. 4 Interestingly, receptor interacting protein kinase 1 (RIPK1) deficiency cause embryonic lethality, suggesting a key role of RIPK1 in host survival. 5 Besides the kinase activity, RIPK1 appears to have a scaffolding function, which may influence immune homeostasis. 6,7 Depending on the interacting partners and posttranslational modifications, RIPK1 has a multifaceted role in cell signaling and cell survival.8 Following TNF-R1 signaling, RIPK1 transitions between pro-survival and pro-cell death signaling complexes. 9,10 Necroptosis is a form of regulated necrosis of cells that operates in the absence of caspase activity 9 and is initiated by the engagement of various TLRs or cytokine receptors.11 The first cardinal signaling step in necrosome signaling is the phosphorylation of RIPK1, which leads to RIPK1-RIPK3 interaction and phosphorylation of RIPK3.12 Although necroptotic signaling has been shown to be...

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TAK1 control of cell death

Cited by 229 publications

References 133 publications

SPATA2 regulates the activation of RIPK1 by modulating linear ubiquitination

SPATA2 regulates the activation of RIPK1 by modulating linear ubiquitination

TAK1 mediates excessive autophagy via p38 and ERK in cisplatin‐induced acute kidney injury

K45A mutation of RIPK1 results in poor necroptosis and cytokine signaling in macrophages, which impacts inflammatory responses in vivo

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