Inhibition of Death Receptor-mediated Gene Induction by a Cycloheximide-sensitive Factor Occurs at the Level of or Upstream of Fas-associated Death Domain Protein (FADD)

Wajant, Harald; Haas, Elvira; Schwenzer, Ralph; Mühlenbeck, Frank; Kreuz, Sebastian; Schubert, G; Grell, Matthias; Smith, Craig A.; Scheurich, Peter

doi:10.1074/jbc.m000811200

Cited by 170 publications

(169 citation statements)

References 45 publications

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“…FLIP proteins also interfere with NFkB activation by TRAIL and Fc-CD95L. 23,24,27,28 Consistent with this, we noticed that cFLIP-S expression abrogated TRAIL-and Fc-CD95L-induced upregulation of the NFkB-regulated target IL8 in HCT116-PIK3CA-mut cells ( Figure 8c). As cFLIP proteins can contribute to tumor cell escape from apoptosis induction by death receptors, these proteins are commonly regarded as tumor-promoting factors.…”

Section: Resultssupporting

confidence: 71%

Mutant PIK3CA licenses TRAIL and CD95L to induce non-apoptotic caspase-8-mediated ROCK activation

et al. 2010

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Constitutively active PI3K catalytic subunit a (PIK3CA) interfered with apoptosis induction downstream of death receptorsignaling complex formation allowing robust caspase-8 activation without triggering the execution steps of apoptosis. In mutant PIK3CA-expressing cells, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and CD95L stimulated nuclear factor kappaB (NFjB) activation, invasion, and transition to an amoeboid-like morphology. NFjB activation and adoption of amoeboid shape were inhibited by caspase-8 knockdown or FLIP-S expression, but only the cell morphology alterations required caspase-8 activity. Furthermore, we identified caspase-8-mediated, caspase-3-independent cleavage of the protein kinase rho-associated, coiled-coil containing protein kinase 1 as a novel mechanism for acquiring amoeboid shape and enhanced invasiveness in response to TRAIL and CD95L. Taken together, we provide evidence that mutated PIK3CA converts the 'tumor surveillance' activity of cancer cell-expressed death receptors and caspase-8 toward tumor promotion.

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Section: Resultssupporting

confidence: 71%

Mutant PIK3CA licenses TRAIL and CD95L to induce non-apoptotic caspase-8-mediated ROCK activation

et al. 2010

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“…A putative role for p53 in the proliferative defect of T cells lacking FADD function 19 has not been confirmed. 18 Evidence that FADD, caspase-8 15,20 and cFLIP [21][22][23] promote T-cell activation by increasing stimulation of NF-kB and c-jun N-terminal kinase (JNK) was not substantiated in other studies. 12,18 Rafts are specialised microdomains, located in the plasma membranes of cells, which have the ability to include or exclude signalling proteins and aggregate in response to various stimuli, thus serving as platforms for signalling complexes.…”

Section: Introductionmentioning

confidence: 91%

Modifications and intracellular trafficking of FADD/MORT1 and caspase-8 after stimulation of T lymphocytes

et al. 2004

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The adaptor protein FADD/MORT1 is essential for apoptosis induced by 'death receptors', such as Fas (APO-1/CD95), mediating aggregation and autocatalytic activation of caspase-8. Perhaps surprisingly, FADD and caspase-8 are also critical for mitogen-induced proliferation of T lymphocytes. We generated novel monoclonal antibodies specific for mouse FADD and caspase-8 to investigate whether cellular responses, apoptosis or proliferation, might be explained by differences in post-translational modification and subcellular localisation of these proteins. During both apoptosis signalling and mitogenic activation, FADD and caspase-8 aggregated in multiprotein complexes and formed caps at the plasma membrane but they did not colocalise with lipid rafts. Interestingly, mitogenic stimulation, but not Fas ligation, induced a unique post-translational modification of FADD. These different modifications may determine whether FADD and caspase-8 induce cell death or proliferation.

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“…Although it has been shown that TRAF1 can be induced by selected stimuli (e.g., IL-1 and members of the TNF ligand family), and activated T and B cells (Mosialos et al, 1995;Lee et al, 1996;Carpentier and Beyaert, 1999;Dunn et al, 1999;Schwenzer et al, 1999;Wajant et al, 2000), the intracellular mechanisms regulating TRAF1 gene expression remain largely undefined.…”

Section: Discussionmentioning

confidence: 99%

Regulation of phorbol ester-mediated TRAF1 induction in human colon cancer cells through a PKC/RAF/ERK/NF-κB-dependent pathway

Wang

et al. 2004

Oncogene

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Tumor necrosis factor (TNF) receptor-associated factors (TRAFs) are cytoplasmic adapter proteins that link a wide variety of cell surface receptors to the apoptotic signaling cascade. The purpose of this study was to delineate the signaling pathways and TRAF1 promoter elements responsible for phorbol ester-mediated TRAF1 induction in human colon cancers. Here, we found that the PKC activators, phorbol 12-myristate 13-acetate (PMA) and bryostatin I, induced TRAF1 mRNA expression; pretreatment with actinomycin D blocked PMA-mediated TRAF1 expression suggesting induction at the transcriptional level. In contrast, expression of other TRAFs (TRAF2, 3 and 4) was minimally altered by PMA. Various PKC isoform-selective inhibitors blocked PMAmediated TRAF1 mRNA and promoter stimulation; rottlerin, a selective PKCd inhibitor, had no effect suggesting that Ca 2 þ -dependent PKC isoforms (e.g., PKCa and bI) play a role in TRAF1 regulation. In addition, the MEK/ERK inhibitors, PD98059 and UO126, suppressed PMA-stimulated TRAF1 promoter activity indicating a role for ERK in TRAF1 induction. Moreover, cotransfection of a dominant-negative Raf-1 (Raf-C4) significantly reduced PMA-stimulated TRAF1 promoter activity whereas transfection of dominantnegative Ras or treatment with Ras inhibitors had minimal to no effect on TRAF1 induction suggesting dependence on Raf, but not Ras, activation. Finally, site-specific mutagenesis of functional NF-jB sites (particularly the most proximal site) in the TRAF1 promoter significantly decreased PMA-mediated promoter activity. In conclusion, our results demonstrate selective induction of TRAF1 in human colon cancer cells through a Ca 2 þ -dependent PKC/Raf-1/ERK/NF-jB-dependent pathway.

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Inhibition of Death Receptor-mediated Gene Induction by a Cycloheximide-sensitive Factor Occurs at the Level of or Upstream of Fas-associated Death Domain Protein (FADD)

Cited by 170 publications

References 45 publications

Mutant PIK3CA licenses TRAIL and CD95L to induce non-apoptotic caspase-8-mediated ROCK activation

Mutant PIK3CA licenses TRAIL and CD95L to induce non-apoptotic caspase-8-mediated ROCK activation

Modifications and intracellular trafficking of FADD/MORT1 and caspase-8 after stimulation of T lymphocytes

Regulation of phorbol ester-mediated TRAF1 induction in human colon cancer cells through a PKC/RAF/ERK/NF-κB-dependent pathway

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