JNK activation is not required for Fas-mediated apoptosis

Low, Walter C.; Smith, Anna; Ashworth, Alan; Collins, Mary

doi:10.1038/sj.onc.1202702

Cited by 28 publications

(20 citation statements)

References 43 publications

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“…6C), demonstrating the efficacy of this JNK inhibitor. These results show that JNK is not required for CCN1/FasL synergism, in concordance with previous findings that JNK is dispensable for Fas-mediated apoptosis in lymphocytes (44). By contrast, the chemical blockers SB202190 and SB203580, which inhibit both p38␣ and p38␤ isoforms, significantly diminished FasL/CCN1-induced apoptosis (Fig.…”

Section: Ccn1 and Ccn2 Synergize With Fasl To Induce Apoptosissupporting

confidence: 81%

Fas-Mediated Apoptosis Is Regulated by the Extracellular Matrix Protein CCN1 (CYR61) In Vitro and In Vivo

Juric

Chen

Lau

2009

Molecular and Cellular Biology

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Although Fas ligand (FasL) is primarily expressed by lymphoid cells, its receptor Fas (CD95/Apo-1) is broadly expressed in numerous nonlymphoid tissues and can mediate apoptosis of parenchymal cells upon injury and infiltration of inflammatory cells. Here we show that CCN1 (CYR61) and CCN2 (CTGF), matricellular proteins upregulated at sites of inflammation and wound repair, synergize with FasL to induce apoptosis by elevating cellular levels of reactive oxygen species (ROS). CCN1 acts through engagement of integrin ␣ 6 ␤ 1 and cell surface heparan sulfate proteoglycans, leading to ROS-dependent hyperactivation of p38 mitogen-activated protein kinase in the presence of FasL to enhance mitochondrial cytochrome c release. We show that CCN1 activates neutral sphingomyelinase, which functions as a key source of CCN1-induced ROS critical for synergism with FasL. Furthermore, Fas-dependent hepatic apoptosis induced by an agonistic monoclonal anti-Fas antibody or intragastric administration of alcohol is severely blunted in knock-in mice expressing an apoptosis-defective Ccn1 allele. These results demonstrate that CCN1 is a physiologic regulator of Fas-mediated apoptosis and that the extracellular matrix microenvironment can modulate Fas-dependent apoptosis through CCN1 expression.

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Section: Ccn1 and Ccn2 Synergize With Fasl To Induce Apoptosissupporting

confidence: 81%

Fas-Mediated Apoptosis Is Regulated by the Extracellular Matrix Protein CCN1 (CYR61) In Vitro and In Vivo

Juric

Chen

Lau

2009

Molecular and Cellular Biology

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“…128 FAS-induced activation of the Jnk pathway is reported to require caspase activation, 129 however, in the IL-3-dependent cell line BAF-3, over-expression of a Jnk specific phosphatase (M3/6) did not effect FAS-mediated apoptosis. 130 These data support the idea that FAS-induced apoptosis may lead to the induction of Jnk activation, but this activation is not required for FAS-induced apoptosis of hematopoietic cells. In contrast to these findings it was reported, using a dominant-negative Jnk, that Jnk activation is required for apoptosis induced by the Rho family member CDC42.…”

Section: The Stress-activated Protein Kinasessupporting

confidence: 77%

Kinases: positive and negative regulators of apoptosis

2000

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Cells sense and respond to extracellular factors via receptors on the cell surface that trigger intracellular signaling pathways. The signals received by the receptors on hematopoietic cells often determine if the cell proliferates, survives or undergoes apoptosis. Apoptosis can be induced by almost any cytotoxic stimuli. These stimuli may be an absence of signals arising from cellular receptors, stimulation of specific ligand receptors on the cell surface, chemotherapeutic agents, and ionizing radiation or oxygen radicals, as well as a number of other factors. Cellular kinases and phosphatases participate in signaling cascades that influence this process. We review the ability of the calmodulin-dependent-kinases, I-B kinases, PI3-kinases, Jakkinases, PKC, PKA, and MAP kinase signaling pathways (Erk, Jnk, and p38), to influence the apoptotic process. In addition, we discuss the cross-talk that exists between signaling cascades that are pro-apoptotic and anti-apoptotic.

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“…JNK activation has been reported to accompany Fas receptor activation. Some studies found that JNK was not required for Fas receptor-mediated apoptosis (Abreu-Martin et al, 1999;Low et al, 1999;Hofmann et al, 2001), but others have shown that JNK activation accelerates Fas-mediated apoptosis in a number of cell lines (Brenner et al, 1997;Yang et al, 1997;Le-Niculescu et al, 1999;Zhang et al, 2000). Our group has previously identified JNK activation as being necessary for Fas-mediated apoptosis in DU 145 cells (CostaPereira et al, 2000;Curtin and Cotter, 2002).…”

Section: Du 145 Prostate Carcinoma Cells Are Resistant To Fas-mediatementioning

confidence: 99%

Defects in death-inducing signalling complex formation prevent JNK activation and Fas-mediated apoptosis in DU 145 prostate carcinoma cells

Curtin

Cotter

2003

Br J Cancer

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Androgen-independent prostate carcinomas are resistant to chemotherapy and cell lines derived from androgen-independent prostate carcinomas such as DU 145 cells are highly resistant to Fas-mediated apoptosis. The incubation of DU 145 cells with anti-Fas IgM agonistic antibody of Fas receptor fails to activate JNK, a stress kinase involved in regulating apoptosis. We have previously shown that JNK activation is sufficient and necessary to promote Fas-mediated apoptosis in DU 145 cells. We investigate the mechanisms by which JNK activation and apoptosis are abrogated. HSP27 is overexpressed in DU 145 cells and has previously been reported to sequester DAXX and prevent JNK activation in cells treated with anti-Fas IgM. However, we find no evidence that HSP27 interacts with DAXX in DU 145 cells. Instead, we find that FADD does not interact with caspase-8 and this results in defective death-inducing signalling complex formation following Fas receptor activation.

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JNK activation is not required for Fas-mediated apoptosis

Cited by 28 publications

References 43 publications

Fas-Mediated Apoptosis Is Regulated by the Extracellular Matrix Protein CCN1 (CYR61) In Vitro and In Vivo

Fas-Mediated Apoptosis Is Regulated by the Extracellular Matrix Protein CCN1 (CYR61) In Vitro and In Vivo

Kinases: positive and negative regulators of apoptosis

Defects in death-inducing signalling complex formation prevent JNK activation and Fas-mediated apoptosis in DU 145 prostate carcinoma cells

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