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

• Verfasst von: Hofmann, Thomas G. [VerfasserIn]
• Verfasst von: Dröge, Wulf [VerfasserIn]
• Titel: CD95-induced JNK activation signals are transmitted by the death-inducing signaling complex (DISC), but not by Daxx
• Verf.angabe: Thomas G. Hofmann, Andreas Möller, Steffen P. Hehner, Dominik Welsch, Wulf Dröge, and M. Lienhard Schmitz
• E-Jahr: 2001
• Jahr: 09 June 2001
• Umfang: 7 S.
• Fussnoten: Gesehen am 03.02.2021
• Titel Quelle: Enthalten in: International journal of cancer
• Ort Quelle: Bognor Regis : Wiley-Liss, 1966
• Jahr Quelle: 2001
• Band/Heft Quelle: 93(2001), 2, Seite 185-191
• ISSN Quelle: 1097-0215
• DOI: doi:10.1002/ijc.1316
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: apoptosis
• Sach-SW: ASK1
• Sach-SW: CD95 receptor
• Sach-SW: DISC
• Sach-SW: JNK
• K10plus-PPN: 1747188905

Abstract

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.