TWEAK, a New Secreted Ligand in the Tumor Necrosis Factor Family That Weakly Induces Apoptosis

Chicheportiche, Yves; Bourdon, Paul; Xu, Haoda; Hsu, Yen-Ming; Scott, Hamish S.; Hession, Catherine; García, Irene; Browning, Jeffrey L.

doi:10.1074/jbc.272.51.32401

Cited by 637 publications

(624 citation statements)

References 53 publications

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“…55,56 We were intrigued by two old reports showing that IFNγ and TWEAK synergise to kill tumour cell lines. 25,26 We confirmed these original observations and found that SMs can also synergise with IFNγ to kill cells. IFNγ can transcriptionally upregulate target genes and this was essential for IFNγ/SM killing because this death could be blocked by SOCS1 overexpression.…”

Section: Discussionsupporting

confidence: 82%

“…24 Earlier reports demonstrated that TWEAK not only synergises with cell death ligands such as TNF, TRAIL and Fas but also with interferon-γ (IFNγ) to kill cancer cells. 25,26 Classical IFNγ receptor signalling, which involves the SOCS1-inhibitable JAK/STAT pathway, 27 differs significantly from typical cell death receptor pathways. It has however been implicated in causing apoptosis, 28,29 and this has been attributed to, among other things, IFNγ-induced upregulation of proapoptotic proteins such as Puma, FasL, TRAIL 27,30,31 and caspase-8.…”

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confidence: 99%

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Combination of IAP antagonist and IFNγ activates novel caspase-10- and RIPK1-dependent cell death pathways

et al. 2017

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Peptido-mimetic inhibitor of apoptosis protein (IAP) antagonists (Smac mimetics (SMs)) can kill tumour cells by depleting endogenous IAPs and thereby inducing tumour necrosis factor (TNF) production. We found that interferon-γ (IFNγ) synergises with SMs to kill cancer cells independently of TNF − and other cell death receptor signalling pathways. Surprisingly, CRISPR/Cas9 HT29 cells doubly deficient for caspase-8 and the necroptotic pathway mediators RIPK3 or MLKL were still sensitive to IFNγ/SMinduced killing. Triple CRISPR/Cas9-knockout HT29 cells lacking caspase-10 in addition to caspase-8 and RIPK3 or MLKL were resistant to IFNγ/SM killing. Caspase-8 and RIPK1 deficiency was, however, sufficient to protect cells from IFNγ/SM-induced cell death, implying a role for RIPK1 in the activation of caspase-10. These data show that RIPK1 and caspase-10 mediate cell death in HT29 cells when caspase-8-mediated apoptosis and necroptosis are blocked and help to clarify how SMs operate as chemotherapeutic agents.

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Section: Discussionsupporting

confidence: 82%

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confidence: 99%

Combination of IAP antagonist and IFNγ activates novel caspase-10- and RIPK1-dependent cell death pathways

et al. 2017

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“…Among the TNF-related cytokines, five ligands bind to death receptors, such as CD95L, TNF, lymphotoxin-␣ (LT␣), TRAIL and TWEAK, which was recently identified as a ligand for DR3/TRAMP. [44][45][46] As suggested by structural and biochemical data, all active ligands consist of three identical subunits and activate their receptors by oligomerization. 14,47 Another common feature is that, with the exception of LT␣, all are type II transmembrane proteins.…”

Section: Structure and Function Of Death Receptorsmentioning

confidence: 99%

The kiss of death: promises and failures of death receptors and ligands in cancer therapy

et al. 2001

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“…Like most TNF superfamily ligands, TWEAK [also known as tumor necrosis factor (ligand) superfamily member 12, CD255, or previously APO3 ligand] is initially synthesized as a type II transmembrane protein that can be cleaved into a soluble cytokine. 9 TWEAK, a noncovalent homotrimer, mediates its activity through binding to a 14-kDA type I transmembrane receptor termed fibroblast growth factor-inducible 14 (Fn14). 10 Fn14 does not possess intrinsic protein kinase activity.…”

mentioning

confidence: 99%

Tumor Necrosis Factor–Like Weak Inducer of Apoptosis Is a Mitogen for Liver Progenitor Cells

Tirnitz–Parker¹,

Viebahn²,

Jakubowski³

et al. 2010

Hepatology

160

182

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Liver progenitor cells (LPCs) represent the cell compartment facilitating hepatic regeneration during chronic injury while hepatocyte-mediated repair mechanisms are compromised. LPC proliferation is frequently observed in human chronic liver diseases such as hereditary hemochromatosis, fatty liver disease, and chronic hepatitis. In vivo studies have suggested that a tumor necrosis factor family member, tumor necrosis factor–like weak inducer of apoptosis (TWEAK), is promitotic for LPCs; whether it acts directly is not known. In our murine choline-deficient, ethionine-supplemented (CDE) model of chronic liver injury, TWEAK receptor [fibroblast growth factor-inducible 14 (Fn14)] expression in the whole liver is massively upregulated. We therefore set out to investigate whether TWEAK/Fn14 signaling promotes the regenerative response in CDE-induced chronic liver injury by mitotic stimulation of LPCs. Fn14 knockout (KO) mice showed significantly reduced LPC numbers and attenuated inflammation and cytokine production after 2 weeks of CDE feeding. The close association between LPC proliferation and activation of hepatic stellate cells in chronic liver injury prompted us to investigate whether fibrogenesis was also modulated in Fn14 KO animals. Collagen deposition and expression of key fibrogenesis mediators were reduced after 2 weeks of injury, and this correlated with LPC numbers. Furthermore, the injection of 2-week-CDE-treated wildtype animals with TWEAK led to increased proliferation of nonparenchymal pan cytokeratin–positive cells. Stimulation of an Fn14-positive LPC line with TWEAK led to nuclear factor kappa light chain enhancer of activated B cells (NFκB) activation and dose-dependent proliferation, which was diminished after targeting of the p50 NFκB subunit by RNA interference. Conclusion: TWEAK acts directly and stimulates LPC mitosis in an Fn14-dependent and NFκB-dependent fashion, and signaling via this pathway mediates the LPC response to CDE-induced injury and regeneration. (Hepatology 2010)

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TWEAK, a New Secreted Ligand in the Tumor Necrosis Factor Family That Weakly Induces Apoptosis

Cited by 637 publications

References 53 publications

Combination of IAP antagonist and IFNγ activates novel caspase-10- and RIPK1-dependent cell death pathways

Combination of IAP antagonist and IFNγ activates novel caspase-10- and RIPK1-dependent cell death pathways

The kiss of death: promises and failures of death receptors and ligands in cancer therapy

Tumor Necrosis Factor–Like Weak Inducer of Apoptosis Is a Mitogen for Liver Progenitor Cells

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