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CD95-induced JNK activation signals are transmitted by the death-inducing signaling complex (DISC), but not by Daxx

Here we investigated CD95-mediated JNK activation pathways and their physiological relevance by employing a variety of cell lines with deficiencies in individual signal transmitting proteins. JNK activation was completely dependent on the activation of caspases in type I and type II cells, as reveal...

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Bibliographische Detailangaben
Hauptverfasser: Hofmann, Thomas G. (VerfasserIn) , Dröge, Wulf (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 09 June 2001
In: International journal of cancer
Year: 2001, Jahrgang: 93, Heft: 2, Pages: 185-191
ISSN:1097-0215
DOI:10.1002/ijc.1316
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1002/ijc.1316
Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.1316
Volltext
Verfasserangaben:Thomas G. Hofmann, Andreas Möller, Steffen P. Hehner, Dominik Welsch, Wulf Dröge, and M. Lienhard Schmitz
Beschreibung
Zusammenfassung:Here we investigated CD95-mediated JNK activation pathways and their physiological relevance by employing a variety of cell lines with deficiencies in individual signal transmitting proteins. JNK activation was completely dependent on the activation of caspases in type I and type II cells, as revealed by the inhibitory effects of the caspase inhibitors zVAD-fmk or the cowpoxvirus-encoded CrmA protein. Jurkat cells deficient in caspase-8 or expressing a dominant negative (DN) form of FADD were unable to induce JNK in response to CD95 ligation, indicating that these death-inducing signaling complex (DISC) proteins are required for signal transmission. Activation of caspases, JNK and apoptosis occurred with a markedly slower kinetics in cells expressing a DN version of ASK1, revealing an important contribution of ASK1 for these processes. A C-terminally truncated version of Daxx impaired CD95-mediated apoptosis without affecting the JNK signal. DN forms of FADD, MKK4 and MKK7 completely inhibited CD95-mediated JNK activation but remained without impact on cell killing, indicating that JNK activation is not required for the execution process of CD95-mediated cell killing.
Beschreibung:Gesehen am 03.02.2021
Beschreibung:Online Resource
ISSN:1097-0215
DOI:10.1002/ijc.1316

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