Editors' ChoiceApoptosis

Another IAP

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Science's STKE  29 Jan 2002:
Vol. 2002, Issue 117, pp. tw49
DOI: 10.1126/stke.2002.117.tw49

Inhibitors of apoptosis proteins (IAPs) block cell death by interacting with and inhibiting caspases. IAP-inhibitory proteins work in opposition to induce cell death. Such inhibitors are present in both mammals and fruit flies, and all contain an amino-terminal IAP binding motif that is thought to disrupt caspase-IAP interaction. Three groups have identified another IAP-inhibitory protein called Sickle (Skl) in Drosophila. Skl is expressed predominantly in the fly central nervous system during development. Like other IAP inhibitors, Skl also interacted with and inhibited the caspase-inhibiting activity of IAPs in vitro. Skl induced cell death when overexpressed in cultured mammalian or fly cells. However, only coexpression of Skl with another IAP-inhibitor caused defective eye development. In a Drosophila mutant that expresses normal amounts of Sickle, but lacks the three other IAP inhibitors, Reaper, Hid, and Grim, there was little observed cell death. The studies suggest that Sickle may synergize with other family members to induce its apoptotic effect.

S. M. Srinivasula, P. Datta, M. Kobayashi, J.-W. Wu, M. Fujioka, R. Hegde, Z. Zhang, R. Mukattash, T. Fernandes-Alnemri, Y. Shi, J. B. Jaynes, E. S. Alnemri, sickle, a novel Drosophila death gene in the reaper/hid/grim regions, encodes an IAP-inhibitory protein. Curr. Biol. 12, 125-130 (2002). [Online Journal]

J. P. Wing, J. S. Karres, J. L. Ogdahl, L. Zhou, L. M. Schwartz, J. R. Nambum, Drosophila sickle is a novel grim-reaper cell death activator. Curr. Biol. 12, 131-135 (2002). [Online Journal]

A. Christich, S. Kauppila, P. Chen, N. Sogame, S.-I. Ho, J. M. Abrams, The damage-responsive Drosophila gene sickle encodes a novel IAP binding protein similar to but distinct from reaper, grim, and hid. Curr. Biol. 12, 137-140 (2002). [Online Journal]

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