TNF Ligands

Drosophila Eiger Triggers Cell Death

Science's STKE  25 Jun 2002:
Vol. 2002, Issue 138, pp. tw222-TW222
DOI: 10.1126/stke.2002.138.tw222

Igaki et al. report the identification of the first Drosophila tumor necrosis factor (TNF) ligand, which they call Eiger and which is most similar to the human ectodyplasin-A protein. Eiger was identified in a genetic screen for genes that when overexpressed cause reduced size of the eye as a consequence of cell death. Overexpression of Eiger in the wing discs completely prevented wing formation. Expression in sensory precursor cells resulted in abnormal bristles, and expression in the abdomen severely impaired development there. These phenotypes are different than those caused by overexpression of Reaper, a protein that stimulates caspase activation in the intrinsic apoptosis pathway. The Eiger-induced reduced eye phenotype was suppressed in the presence of Drosophila inhibitor of apoptosis protein 1 (DIAP1) But it was unaffected in the presence of the caspase inhibitory protein P35 from baculovirus or in the presence of a dominant-negative form of the caspase DRONC. These genetic interactions are unlike those of Reaper. Eiger stimulated cell death and did activate caspases when expressed in the eye, although the extent and location of the caspase activation again differed from that produced by Reaper. In flies with mutations or decreased expression of components of the Jun NH2-terminal kinase (JNK) pathway, the reduced-eye phenotype induced by Eiger was suppressed. Additionally, overexpression of Eiger stimulated the phosphorylation of Drosophila JNK (known as Basket) and stimulated the expression of a target gene of the JNK pathway that encodes Puckered (a phosphatase). The authors propose that Eiger stimulates cell death through caspase-dependent and caspase-independent mechanisms and that the latter rely on activation of the JNK pathway.

T. Igaki, H. Kanda, Y. Yamamoto-Goto, H. Kanuka, E. Kuranaga, T. Aigaki, M. Miura, Eiger, a TNF superfamily ligand that triggers the Drosophila JNK pathway. EMBO J. 21, 3009-3018 (2002). [Abstract] [Full Text]