Catalytically active Yersinia outer protein P induces cleavage of RIP and caspase-8 at the level of the DISC independently of death receptors in dendritic cells

Gröbner, Sabine; Adkins, Irena; Schulz, Sebastian; Richter, Kathleen; Borgmann, Stefan; Wesselborg, Sebastian; Ruckdeschel, Klaus; Micheau, Olivier; Autenrieth, Ingo B.

doi:10.1007/s10495-007-0100-x

Cited by 30 publications

(29 citation statements)

References 78 publications

(109 reference statements)

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“…Caspase-8 has been described to be activated in an FADDdependent manner with some stimuli, in the absence of death receptor-ligand interactions. 37, 38 We have not been able to Caspase-8-dependent apoptosis by lack of glucose A Caro-Maldonado et al obtain conclusive results regarding the involvement of FADD as the adapter protein for caspase-8 activation after glucose deprivation. We cannot exclude that, upon glucose removal, endogenous FADD may be aggregated intracellularly, interacting with caspase-8 and promoting its activation.…”

Section: Discussionmentioning

confidence: 88%

Glucose deprivation induces an atypical form of apoptosis mediated by caspase-8 in Bax-, Bak-deficient cells

et al. 2010

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Apoptosis induced by most stimuli proceeds through the mitochondrial pathway. One such stimulus is nutrient deprivation. In this study we studied death induced by glucose deprivation in cells deficient in Bax and Bak. These cells cannot undergo mitochondrial outer membrane permeabilization (MOMP) during apoptosis, but they undergo necrosis when treated with MOMPdependent apoptotic stimuli. We find in these cells that glucose deprivation, rather than inducing necrosis, triggered apoptosis. Cell death required caspase activation as inhibition of caspases with peptidic inhibitors prevented death. Glucose deprivationinduced death displayed many hallmarks of apoptosis, such as caspase cleavage and activity, phosphatidyl-serine exposure and cleavage of caspase substrates. Neither overexpression of Bcl-xL nor knockdown of caspase-9 prevented death. However, transient or stable knockdown of caspase-8 or overexpression of CrmA inhibited apoptosis. Cell death was not inhibited by preventing death receptor-ligand interactions, by overexpression of c-FLIP or by knockdown of RIPK1. Glucose deprivation induced apoptosis in the human tumor cell line HeLa, which was prevented by knockdown of caspase-8. Thus, we have found that glucose deprivation can induce a death receptor-independent, caspase-8-driven apoptosis, which is engaged to kill cells that cannot undergo MOMP. Apoptosis is a form of cell death required for homeostasis of human tissues. Apoptotic cells display several morphological and biochemical changes, which are a consequence of the activity of caspase proteases.1 Caspases are normally inactive in the cytosol, but they become activated by dimerization and/or proteolysis by other caspases. 'Executioner' caspases such as caspase-3 are activated through cleavage by 'initiator' or 'apical' caspases, of which the best characterized are caspases-8 and -9. Caspase-8 is activated by its recruitment to the multimeric DISC (death-inducing signaling complex) in response to extracellular ligands such as Fas/CD95-ligand, TRAIL or TNF; 2 this is the death receptor, or extrinsic pathway of apoptosis. Caspase-9 is activated by dimerization after recruitment to the apoptosome, a complex of APAF1 proteins formed in response to the release of the mitochondrial protein cytochrome c into the cytosol. 3 This caspase activation cascade is called the mitochondrial or intrinsic pathway of apoptosis.The mitochondrial pathway of apoptosis is regulated by proteins of the Bcl-2 family, which regulate the integrity of the mitochondrial outer membrane, thereby controlling cytochrome c and subsequent caspase activation.4 Impairment of the mitochondrial pathway is common in human tumors. Cancer cells frequently overexpress the antiapoptotic proteins Bcl-2, Bcl-xL and Mcl-1, or they lack functional proapoptotic Bcl-2 family members, including Bax, Bak or both. 5 The overexpression of antiapoptotic Bcl-2 proteins not only blocks the morphological features of apoptosis, but also enables clonogenic cell survival. 6 For these reasons, cells from Bax, B...

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Section: Discussionmentioning

confidence: 88%

Glucose deprivation induces an atypical form of apoptosis mediated by caspase-8 in Bax-, Bak-deficient cells

et al. 2010

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“…Signaling to the transcription factor NF-κB controls the transcription of cytokines such as IL-6, TNF, pro-IL-1β, and pro-IL-18, and stimulates cell survival. Y. pestis can induce cell death in macrophages and dendritic cells via the type III secretion system (T3SS) effector Yersinia outer protein J (YopJ; YopP in Yersinia enterocolitica), although it is unclear whether this is entirely by apoptosis (11,12). All human-pathogenic Yersiniae (Y. pestis, Yersinia pseudotuberculosis, and Y. enterocolitica) harbor cytotoxic properties toward host cells, and YopJ production is associated with cell death in vivo and in vitro (13)(14)(15)(16).…”

mentioning

confidence: 99%

Caspase-8 and RIP kinases regulate bacteria-induced innate immune responses and cell death

Weng

Marty-Roix

Ganesan

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

263

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A number of pathogens cause host cell death upon infection, and Yersinia pestis, infamous for its role in large pandemics such as the "Black Death" in medieval Europe, induces considerable cytotoxicity. The rapid killing of macrophages induced by Y. pestis, dependent upon type III secretion system effector Yersinia outer protein J (YopJ), is minimally affected by the absence of caspase-1, caspase-11, Fas ligand, and TNF. Caspase-8 is known to mediate apoptotic death in response to infection with several viruses and to regulate programmed necrosis (necroptosis), but its role in bacterially induced cell death is poorly understood. Here we provide genetic evidence for a receptor-interacting protein (RIP) kinasecaspase-8-dependent macrophage apoptotic death pathway after infection with Y. pestis, influenced by Toll-like receptor 4-TIR-domain-containing adapter-inducing interferon-β (TLR4-TRIF). Interestingly, macrophages lacking either RIP1, or caspase-8 and RIP3, also had reduced infection-induced production of IL-1β, IL-18, TNF, and IL-6; impaired activation of the transcription factor NF-κB; and greatly compromised caspase-1 processing. Cleavage of the proform of caspase-1 is associated with triggering inflammasome activity, which leads to the maturation of IL-1β and IL-18, cytokines important to host responses against Y. pestis and many other infectious agents. Our results identify a RIP1-caspase-8/RIP3-dependent caspase-1 activation pathway after Y. pestis challenge. Mice defective in caspase-8 and RIP3 were also highly susceptible to infection and displayed reduced proinflammatory cytokines and myeloid cell death. We propose that caspase-8 and the RIP kinases are key regulators of macrophage cell death, NF-κB and inflammasome activation, and host resistance after Y. pestis infection.

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“…caspase-3) to induce apoptosis [97] . YopP/ J-mediated inhibition of the MAPK and NFκB signaling pathways, along with Toll-like receptor 4 signaling, induces apoptosis of macrophages and dendritic cells [98][99][100][101][102] . This reported YopJ-induced cellular apoptosis was shown to be a result of signal transduction via the receptor-interacting Ser/Thr kinase 1 (RIPK1), Fas-associated death domain and caspase-8 signaling cascade to induce apoptosis [103,104] .…”

Section: Yopp/j Induces Apoptosis Through Caspase-8mentioning

confidence: 99%

“…YopP/J activity affects macrophages, dendritic cells, NK cells, and to varying degrees neutrophils [90,98,[109][110][111] . However, activity of YopP/J in vivo varies depending on the Yersinia strain, YopP/J variant, experimental para-meters, and infection model [62,92,[112][113][114][115] .…”

Section: Yopp/j Utilizes Host Signaling Pathways To Promote Yersinia mentioning

confidence: 99%

“…Nevertheless, translocation of YopP/J results in the inhibition of key signaling pathways that mediate a proinflammatory response, and also induces production of specific cytokines [83,89,[116][117][118] . In particular is the well established observation that YopJ activity on the MAPK and NFκB signaling pathways mediates the maturation of caspase-1 [98,[103][104][105] . Activated caspase-1 cleaves pro-IL-18 and pro-IL-1β to produce active IL-18 and IL-1β [39] .…”

Section: Yopp/j Utilizes Host Signaling Pathways To Promote Yersinia mentioning

confidence: 99%

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Yersiniatype III effectors perturb host innate immune responses

Pha

Navarro

2016

WJBC

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The innate immune system is the first line of defense against invading pathogens. Innate immune cells recognize molecular patterns from the pathogen and mount a response to resolve the infection. The production of proinflammatory cytokines and reactive oxygen species, phagocytosis, and induced programmed cell death are processes initiated by innate immune cells in order to combat invading pathogens. However, pathogens have evolved various virulence mechanisms to subvert these responses. One strategy utilized by Gram-negative bacterial pathogens is the deployment of a complex machine termed the type Ⅲ secretion system (T3SS). The T3SS is composed of a syringe-like needle structure and the effector proteins that are injected directly into a target host cell to disrupt a cellular response. The Multisite autophosphorylation by YpkA to activate its kinase domain was also shown and postulated to serve as a mechanism to bypass regulation by host phosphatases. In addition, novel Yersinia effector protein targets, such as caspase-1, and signaling pathways including activation of the inflammasome were identified. In this review, we summarize the recent discoveries made on Yersinia effector proteins and their contribution to Yersinia pathogenesis.

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Catalytically active Yersinia outer protein P induces cleavage of RIP and caspase-8 at the level of the DISC independently of death receptors in dendritic cells

Cited by 30 publications

References 78 publications

Glucose deprivation induces an atypical form of apoptosis mediated by caspase-8 in Bax-, Bak-deficient cells

Glucose deprivation induces an atypical form of apoptosis mediated by caspase-8 in Bax-, Bak-deficient cells

Caspase-8 and RIP kinases regulate bacteria-induced innate immune responses and cell death

Yersiniatype III effectors perturb host innate immune responses

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