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Sci. Signal., 25 October 2011
Vol. 4, Issue 196, p. ec298
[DOI: 10.1126/scisignal.4196ec298]

EDITORS' CHOICE

Structural Biology Allowing Apoptosis

Valda K. Vinson

Science, AAAS, Washington, DC 20005, USA

Inhibitor of apoptosis (IAP) proteins hold the caspases in check that trigger cell death. They are a target for cancer therapy, because many cancer cells resist cytotoxic treatments by overexpressing IAPs. A drug design strategy is to mimic natural ligands that induce IAP autoubiquitination and subsequent degradation. Dueber et al. describe structural and biochemical studies that show how IAP is activated for degradation. In unliganded IAP, the catalytic RING domains are sequestered in a compact monomer. Antagonist binding to the baculovirus IAP repeat domain promotes conformational changes that drive RING domain dimerization, which is required for ubiquitination.

E. C. Dueber, A. J. Schoeffler, A. Lingel, J. M. Elliott, A. V. Fedorova, A. M. Giannetti, K. Zobel, B. Maurer, E. Varfolomeev, P. Wu, H. J. A. Wallweber, S. G. Hymowitz, K. Deshayes, D. Vucic, W. J. Fairbrother, Antagonists induce a conformational change in cIAP1 that promotes autoubiquitination. Science 334, 376–380 (2011). [Abstract] [Full Text]

Citation: V. K. Vinson, Allowing Apoptosis. Sci. Signal. 4, ec298 (2011).



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