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Nachmias B, Ashhab Y, Ben Yehuda DThe inhibitor of apoptosis protein family (IAPs): an emerging therapeutic target in cancer. Semin Cancer Biol 14:231-243

Department of Hematology, Hadassah University Hospital, Ein-Karem, P.O.B. 12000, Jerusalem 91120, Israel.
Seminars in Cancer Biology (Impact Factor: 9.33). 09/2004; 14(4):231-43. DOI: 10.1016/j.semcancer.2004.04.002
Source: PubMed

ABSTRACT

Apoptosis is a crucial biological process that prevents uncontrolled cell proliferation and eliminates harmful cells. Resistance to apoptotic stimuli is a hallmark feature of various cancers. One of the mechanisms through which tumor cells are believed to acquire resistance to apoptosis is by overexpression of inhibitor of apoptosis proteins (IAPs). IAPs are a group of structurally related proteins that were initially identified in baculoviruses. Mammalian IAPs block apoptosis either by binding and inhibiting caspases or through caspase-independent mechanisms. This family of proteins has become increasingly prominent in the field of cancer biology. To date, overexpression of several IAPs has been detected in various cancers. This paper reviews the recent advances in the research of IAPs. The differential expression and the biological significance of each IAP in various cancer types will be discussed. Finally, we review the most recent advances in the research efforts aimed at using IAPs as potential targets for cancer therapy.

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    • "Several IAP proteins have been shown to regulate apoptosis in a Caspase-independent manner through the JNK or NF-κB signaling pathways (38–40). Interestingly, IAPs function as E3 ubiquitin ligases and can target cellular proteins for proteasomal degradation, this process being essential for apoptosis (41). IAPs activities are regulated by second mitochondria derived activator of Caspases (smac) (42). "
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    • "A common polymorphism at the survivin gene promoter -31G/C has been shown to influence survivin expression and the risk for cancer. Studies carried out in tissue have suggested that survivin may have a critical role in the diagnosis, prognosis, and prediction of response to therapy (Altieri et al., 2003;Nachmias et al., 2004;Shinohara et al., 2005). The genetic variant -31G/C in the survivin promoter region has been associated with the overexpression of survivin at both the protein and the messenger RNA levels in cancer cells. "
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    • "Defective apoptotic signaling pathways have an important role in the initiation and progression of cancer (Reed, 1999). One of the mechanisms through which tumor cells are believed to acquire resistance to apoptosis is overexpression of XIAP, which prevent apoptosis by specifically inhibiting caspases 3, 7, and 9 (Nachmias et al., 2004). Bcl-xL is an anti-apoptotic protein and a member of the Bcl-2 family, which includes Bcl-2, Bcl-w, Bcl-xs, and Mcl-1. "
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