Fas activates NF-κB and induces apoptosis in T-cell lines by signaling pathways distinct from those induced by TNF-α

Packham, Graham; Lahti, Jill M.; Fee, Brian E.; Gawn, Jonathan M.; Coustan‐Smith, Elaine; Campana, Dario; Douglas, Iris; Kidd, Vincent J.; Ghosh, Sankar; Cleveland, John L.

doi:10.1038/sj.cdd.4400217

Cited by 23 publications

(16 citation statements)

References 62 publications

(103 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5) differ substantially from those of TNF-␣ where maximum nuclear translocation could be seen 20 -30 min or earlier (data not shown). Our data regarding the kinetics of Fas-and TNF-induced NF-B activation confirm, in part, those of another direct comparison of Fas and TNF (9), and suggest that pathway intermediates in Fas-induced NF-B activation may differ from those of TNF or other death receptors. Another molecule which associates with the cytoplasmic region of Fas is FAP-1.…”

Section: Discussionsupporting

confidence: 73%

“…Nevertheless, ligation of Fas killed these cells, and condensed and fragmented apoptotic nuclei also were immunoreactive for p65, directly dissociating the Fas-mediated NF-B activation from protection. Similarly, stimulation of TNFR or Fas on the surface of CEM-C7 T cells led not only to the activation of NF-B, but to apoptotic death of the cells (9). Most recently, EMSA, as well as microarray analyses of the transcriptional effects of anti-Fas (and TNF-␣) induction of HT29 colon carcinoma cells, confirmed activation of NF-B (p65/p50) by Fas ligation (45).…”

Section: Discussionmentioning

confidence: 73%

“…Fas (CD95/Apo-1) is a member of the TNFR family of proteins, but the ability of Fas to activate NF-B has been variably reported (5,6) and dissociated from any protective effect (6 -10). Indeed, death occurs in these cell types despite the activation of NF-B (9,10), and inhibition of NF-B has little effect on apoptosis (7). In leukemic or neoplastic cells, resistance to Fas has been attributed to deficiencies in constituents of the Fas pathway, including decreased surface expression of Fas (11), or to the presence of increased levels of antiapoptotic proteins such as Fas-associated phosphatase-1 (FAP-1) 3 (12) or certain members of the Bcl-2 family (13).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Fas Resistance of Leukemic Eosinophils Is Due to Activation of NF-κB by Fas Ligation

Qin

Camoretti-Mercado

Blokh

et al. 2002

The Journal of Immunology

View full text Add to dashboard Cite

TNF family receptors can lead to the activation of NF-κB and this can be a prosurvival signal in some cells. Although activation of NF-κB by ligation of Fas (CD95/Apo-1), a member of the TNFR family, has been observed in a few studies, Fas-mediated NF-κB activation has not previously been shown to protect cells from apoptosis. We examined the Fas-induced NF-κB activation and its antiapoptotic effects in a leukemic eosinophil cell line, AML14.3D10, an AML14 subline resistant to Fas-mediated apoptosis. EMSA and supershift assays showed that agonist anti-Fas (CH11) induced nuclear translocation of NF-κB heterodimer p65(RelA)/p50 in these cells in both a time- and dose-dependent fashion. The influence of NF-κB on the induction of apoptosis was studied using pharmacological proteasome inhibitors and an inhibitor of IκBα phosphorylation to block IκBα dissociation and degradation. These inhibitors at least partially inhibited NF-κB activation and augmented CH11-induced cell death. Stable transfection and overexpression of IκBα in 3D10 cells inhibited CH11-induced NF-κB activation and completely abrogated Fas resistance. Increases in caspase-8 and caspase-3 cleavage induced by CH11 and in consequent apoptotic killing were observed in these cells. Furthermore, while Fas-stimulation of resistant control 3D10 cells led to increases in the antiapoptotic proteins cellular inhibitor of apoptosis protein-1 and X-linked inhibitor of apoptosis protein, Fas-induced apoptosis in IκBα-overexpressing cells led to the down-modulation of both of these proteins, as well as that of the Bcl-2 family protein, Bcl-xL. These data suggest that the resistance of these leukemic eosinophils to Fas-mediated killing is due to induced NF-κB activation.

show abstract

Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 73%

mentioning

confidence: 99%

See 1 more Smart Citation

Fas Resistance of Leukemic Eosinophils Is Due to Activation of NF-κB by Fas Ligation

Qin

Camoretti-Mercado

Blokh

et al. 2002

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…The suppression of the growth of CD34 + myeloid cells by TNF also correlated with the NF-κB activation . Apart from this, Fas activates NF-κB and induces apoptosis in T-cell lines by signaling pathways that are distinct from those induced by TNFα (Packham et al, 1997). Human melanoma cells are protected against UV-induced apoptosis through the down-regulation of NF-κB activity and Fas expression (Ivanov and Ronai, 2000).…”

Section: Pro-apoptotic Activity Of Nf-κbmentioning

confidence: 99%

Nuclear Factor-κB Activation: A Question of Life or Death

Shishodia¹,

Aggarwal²

2002

BMB Reports

206

168

View full text Add to dashboard Cite

Apoptosis is a mode of cell death that plays an important role in both pathological and physiological processes. Research during the last decade has delineated the entire machinery needed for cell death, and its constituents were found to pre-exist in cells. The apoptotic cascade is triggered when cells are exposed to an apoptotic stimulus. It has been known for several years that inhibitors of protein synthesis can potentiate apoptosis that is induced by cytokines and other inducers. Until 1996, it was not understood why protein synthesis inhibitors potentiate apoptosis. Then three reports appeared that suggested the role of the transcription factor NF-κB activation in protecting the cells from TNF-induced apoptosis. Since then several proteins have been identified that are regulated by NF-κB and are involved in cell survival, proliferation, and protection from apoptosis. It now seems that when a cell is attacked by an apoptotic stimulus, the cell responds first by activating anti-apoptotic mechanisms, which may or may not be followed by apoptosis. Whether or not a cell undergoes proliferation, the survival, or apoptosis, appears to involve a balance between the two mechanisms. Inhibitors of protein synthesis seem to suppress the appearance of protein that are involved in anti-apoptosis. The present review discusses how NF-κB controls apoptosis.

show abstract

“…However, there were also conflicting data showing that there was upregulation of TRAIL receptors in peripheral T cells upon activation, but these cells remained resistant to TRAIL [119]. TNF has also been suggested by some studies to play a role in AICD [126,143,144]. It was found that TCR stimulation can induce the expression of TNF [145] and antibody to TNF can partially inhibit antigen induced cell death of T cells in vivo [126].…”

Section: Activation-induced Cell Deathmentioning

confidence: 99%

Apoptosis signaling pathways and lymphocyte homeostasis

2007

View full text Add to dashboard Cite

It has been almost three decades since the term "apoptosis" was first coined to describe a unique form of cell death that involves orderly, gene-dependent cell disintegration. It is now well accepted that apoptosis is an essential life process for metazoan animals and is critical for the formation and function of tissues and organs. In the adult mammalian body, apoptosis is especially important for proper functioning of the immune system. In recent years, along with the rapid advancement of molecular and cellular biology, great progress has been made in understanding the mechanisms leading to apoptosis. It is generally accepted that there are two major pathways of apoptotic cell death induction: extrinsic signaling through death receptors that leads to the formation of the death-inducing signaling complex (DISC), and intrinsic signaling mainly through mitochondria which leads to the formation of the apoptosome. Formation of the DISC or apoptosome, respectively, activates initiator and common effector caspases that execute the apoptosis process. In the immune system, both pathways operate; however, it is not known whether they are sufficient to maintain lymphocyte homeostasis. Recently, new apoptotic mechanisms including caspase-independent pathways and granzyme-initiated pathways have been shown to exist in lymphocytes. This review will summarize our understanding of the mechanisms that control the homeostasis of various lymphocyte populations.

show abstract

Fas activates NF-κB and induces apoptosis in T-cell lines by signaling pathways distinct from those induced by TNF-α

Cited by 23 publications

References 62 publications

Fas Resistance of Leukemic Eosinophils Is Due to Activation of NF-κB by Fas Ligation

Fas Resistance of Leukemic Eosinophils Is Due to Activation of NF-κB by Fas Ligation

Nuclear Factor-κB Activation: A Question of Life or Death

Apoptosis signaling pathways and lymphocyte homeostasis

Contact Info

Product

Resources

About