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Papers In Press, published online ahead of print June 24, 2004
J. Biol. Chem, 10.1074/jbc.C400236200
Submitted on May 25, 2004
Revised on June 24, 2004
Accepted on June 24, 2004

A IAP-IAP complex inhibits apoptosis

Takehiko Dohi, Kazu Okada, Fang Xia, Casey E. Wilford, Temesgen Samuel, Kate Welsh, Hiroyouki Marusawa, Hua Zou, Robert Armstrong, Shu-ichi Matsuzawa, Guy S. Salvesen, John C. Reed, and Dario C. Altieri

Department of Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605

Corresponding Author: dario.altieri{at}umassmed.edu

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 a IAP-IAP complex regulates apoptosis.


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