Inhibitors of Apoptotic Proteins: New Targets for Anticancer Therapy

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Abstract

Inhibitors of apoptotic proteins (IAPs) can play an important role in inhibiting apoptosis by exerting their negative action on caspases (apoptotic proteins). There are eight proteins in this family: NAIP/BIRC1/NLRB, cellular IAP1 (cIAP1)/human IAP2/BIRC2, cellular IAP2 (cIAP2)/human IAP1/BIRC3, X-linked IAP (XIAP)/BIRC4, survivin/BIRC5, baculoviral IAP repeat (BIR)-containing ubiquitin-conjugating enzyme/apollon/BIRC6, livin/melanoma-IAP (ML-IAP)/BIRC7/KIAP, and testis-specific IAP (Ts-IAP)/hILP-2/BIRC8. Deregulation of these inhibitors of apoptotic proteins (IAPs) may push cell toward cancer and neurodegenerative disorders. Inhibitors of apoptotic proteins (IAPs) may provide new target for anticancer therapy. Drugs may be developed that are inhibiting these IAPs to induce apoptosis in cancerous cells.

(1) Mitochondria releases cytochrome C (Cyt C) which binds with ATP and Apaf-1 (2), apaf-1 binds with caspase 9 and activate it (3), activated caspase 9 causes cleavage and activation of caspase 3 (4), (7) BIRC4 present in the cytosol in sufficient amount binds with activated caspase 9 (5) and inhibits the activation of caspase 3 by caspase 9. As shown in this model, mitochondria releases Diablo\smac dimmers which make complex with BIRC4 and in this way caspase 9 become free and can activate caspase 3.

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