Reawakening the cellular death program in neoplasia through the therapeutic blockade of IAP function
Casey W. Wright, Colin S. Duckett
Casey W. Wright, Colin S. Duckett
Published October 3, 2005
Citation Information: J Clin Invest. 2005;115(10):2673-2678. https://doi.org/10.1172/JCI26251.
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Review Series

Reawakening the cellular death program in neoplasia through the therapeutic blockade of IAP function

Abstract

Recent studies have shown that members of the inhibitor of apoptosis (IAP) protein family are highly expressed in several classes of cancer. The primary implication of these findings is that the elevated expression of IAPs is not coincidental but actually participates in oncogenesis by helping to allow the malignant cell to avoid apoptotic cell death. This concept, together with the discovery of several IAP-regulatory proteins that use a conserved mode of action, has stimulated a major effort by many research groups to devise IAP-targeting strategies as a means of developing novel antineoplastic drugs. In this Review, we consider the evidence both for and against the IAPs being valid therapeutic targets, and we describe the types of strategies being used to neutralize their functions.

Authors

Casey W. Wright, Colin S. Duckett

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Figure 1

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The IAP family members. (A) All IAP members contain 1 or more imperfect ...
The IAP family members. (A) All IAP members contain 1 or more imperfect baculovirus iap repeats (BIRs), the defining motif of the IAP family. Many of the IAP proteins also posses an E3 ubiquitin ligase RING domain at the carboxy terminus. (B) XIAP can bind and enzymatically inhibit caspase-3, caspase-7, and caspase-9. XIAP binds caspase-3 and caspase-7 at a sequence directly upstream of BIR2, while it binds caspase-9 in a region of BIR3. CARD, caspase recruitment domain.