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CD95‐induced JNK activation signals are transmitted by the death‐inducing signaling complex (DISC), but not by Daxx
Author(s) -
Hofmann Thomas G.,
Möller Andreas,
Hehner Steffen P.,
Welsch Dominik,
Dröge Wulf,
Schmitz M. Lienhard
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.1316
Subject(s) - fadd , death associated protein 6 , microbiology and biotechnology , fas receptor , jurkat cells , caspase , apoptosis , signal transduction , programmed cell death , caspase 8 , biology , chemistry , immunology , biochemistry , nuclear protein , t cell , immune system , gene , transcription factor
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. © 2001 Wiley‐Liss, Inc.