1. Evolution of TNF Signaling Mechanisms: JNK-Dependent Apoptosis Triggered by Eiger, the Drosophila Homolog of the TNF Superfamily
- Author
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Moreno, Eduardo, Yan, Minhong, and Basler, Konrad
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TUMOR necrosis factors , *CELLULAR control mechanisms , *APOPTOSIS - Abstract
Much of what we know about apoptosis in human cells stems from pioneering genetic studies in the nematode C. elegans . However, one important way in which the regulation of mammalian cell death appears to differ from that of its nematode counterpart is in the employment of TNF and TNF receptor superfamilies . No members of these families are present in C. elegans, yet TNF factors play prominent roles in mammalian development and disease . Here, we describe the cloning and characterization of Eiger, a unique TNF homolog in Drosophila. Like a subset of mammalian TNF proteins, Eiger is a potent inducer of apoptosis. Unlike its mammalian counterparts, however, the apoptotic effect of Eiger does not require the activity of the caspase-8 homolog DREDD, but it completely depends on its ability to activate the JNK pathway. Eiger-induced cell death requires the caspase-9 homolog DRONC and the Apaf-1 homolog DARK. Our results suggest that primordial members of the TNF superfamily can induce cell death indirectly by triggering JNK signaling, which, in turn, causes activation of the apoptosome. A direct mode of action via the apical FADD/caspase-8 pathway may have been coopted by some TNF signaling systems only at subsequent stages of evolution. [Copyright &y& Elsevier]
- Published
- 2002
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