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J. Biol. Chem., Vol. 279, Issue 33, 34087-34090, August 13, 2004
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**
From the
Department of Cancer Biology and the Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts 01605, ¶The Burnham Institute, La Jolla, California 92037, and the ||IDUN Pharmaceuticals, San Diego, California 92121
Regulators of apoptosis are thought to work in concert, but the molecular interactions of this process are not understood. Here, we show that in response to cell death stimulation, survivin, a member of the inhibitor of apoptosis (IAP) gene family, associates with another IAP protein, XIAP, via conserved baculovirus IAP repeats. Formation of a survivin-XIAP complex promotes increased XIAP stability against ubiquitination/proteasomal destruction and synergistic inhibition of apoptosis, which is abolished in XIAP–/– cells. Therefore, orchestration of an IAP-IAP complex regulates apoptosis.
Received for publication, May 25, 2004 , and in revised form, June 24, 2004.
* This work was supported by National Institutes of Health Grants HL54131, CA78810, and CA90917 (to D. C. A.) and AG15393 (to G. S. S. and J. C. R.) and by the Department of Defense Prostate Cancer Research Program, postdoctoral fellowship program. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
These authors contributed equally to this work.
** To whom correspondence should be addressed: University of Massachusetts Medical School, LRB428, 364 Plantation St., Worcester, MA 01605. Tel.: 508-856-5775; Fax: 508-856-5792; E-mail: dario.altieri{at}umassmed.edu.
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