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Neuregulins (NDF, heregulin, GGF ARIA, or SMDF) are EGF-like growth and differentiation factors that signal through tyrosine kinase receptors of the ErbB family. Here, we report a novel phenotype in mice with targeted mutations in the erbB2, erbB3, or neuregulin-1 genes. These three mutations cause a severe hypoplasia of the primary sympathetic ganglion(More)
Upon stimulation, CD95 (APO-1/Fas) recruits the adapter molecule FADD/MORT1, procaspase-8, and the cellular FLICE-inhibitory proteins (c-FLIP) into the death-inducing signaling complex (DISC). According to the induced proximity model, procaspase-8 is activated in the DISC in an autoproteolytic manner by two subsequent cleavage steps. c-FLIP proteins exist(More)
Cell death is executed along several pathways. Apart from necrotic cell death occurring upon tissue injury, several distinct types of apoptosis have been observed. Apoptosis, or programmed cell death, is critical for tissue homeostasis in mul-ticellular organisms. It plays an important role in many physiological processes, especially in development and in(More)
Apoptosis or programmed cell death can be induced by a variety of stimuli including activation of death receptors. This subgroup of the TNF/NGF-receptor-superfamily activates caspases, a family of aspartyl-specific cysteine-proteases, which are the main executioners of apoptosis. Depending on the cell type, signalling pathways downstream of the death(More)
IFN regulatory factors (IRFs) constitute a family of transcription factors that are involved in IFN signaling and the development and differentiation of the immune system. Targeted gene disruption studies in mice assigned their primary role to the immune system. Two lymphoid-specific IRF members, IFN consensus sequence binding protein (ICSBP) and IRF-4,(More)
Stimulation of CD95 leads to oligomerization of this receptor and the recruitment of the Fas-associated death domain (FADD) and procaspase-8 to form the death-inducing signaling complex (DISC). Subsequent proteolytic activation of caspase-8 at the DISC leads to the activation of downstream caspases and execution of apoptosis. The anticancer drug(More)
The rad10, rad16, rad20, and swi9 mutants of the fission yeast Schizosaccharomyces pombe, isolated by their radiation sensitivity or abnormal mating-type switching, have been shown previously to be allelic. We have cloned DNA correcting the UV sensitivity or mating-type switching phenotype of these mutants and shown that the correcting DNA is encompassed in(More)
Efficient activation of antigen-specific T cells requires co-stimulatory signals provided e.g. by CD28. Re-exposure to antigen and CD28 co-stimulation reduces activation-induced cell death (AICD) and increases the number of T cells performing effector functions. AICD is mediated predominantly by CD95 (APO-1/Fas) and its cognate ligand (CD95L). In an in(More)
Interferon (IFN) regulatory factors (IRFs) are a family of transcription factors among which are IRF-1, IRF-2, and IFN consensus sequence binding protein (ICSBP). These factors share sequence homology in the N-terminal DNA-binding domain. IRF-1 and IRF-2 are further related and have additional homologous sequences within their C-termini. Whereas IRF-2 and(More)
Expression of the tumor suppressor IRF-1 results in the inhibition of cell growth and transcriptional activation of the IFN-beta gene. IFN production is not responsible for the IRF-1 mediated cell growth inhibition. It is shown here that activation of the IRF-1 causes induction of PKR expression. PKR is a serine/threonine kinase with tumor suppressor(More)