A potential role of X-linked inhibitor of apoptosis protein in mitochondrial membrane permeabilization and its implication in cancer therapy. Issue 1 (January 2016)

• Record Type: Journal Article
• Authors: Chaudhary, Ajay K.; Yadav, Neelu; Bhat, Tariq A.; O'Malley, Jordan; Kumar, Sandeep; Chandra, Dhyan
• Is Part Of: Drug discovery today. Volume 21:Issue 1(2016)
• Page Start: 38
• Page End: 47
• Publication Date: 2016-01
• Subjects: Drugs -- Design -- Periodicals; Drugs -- Research -- Periodicals; 615.1
• DOI: 10.1016/j.drudis.2015.07.014
• Languages: English
• ISSNs: 1359-6446

Abstract

Highlights: XIAP harbors prosurvival, proapoptotic and nonapoptotic functions. Proapoptotic BH3-only protein Bim can regulate XIAP translocation to mitochondria. XIAP induces Bax-dependent permeabilization of the mitochondrial membrane. XIAP translocation to mitochondria associates with mitochondrial ubiquitination. Targeting the mitochondrial permeabilization function of XIAP could provide novel cancer therapeutics. Abstract : X-chromosome-linked inhibitor of apoptosis protein (XIAP) has an important regulatory role in programmed cell death by inhibiting the caspase cascade. Activation of XIAP-dependent signaling culminates into regulation of multiple cellular processes including apoptosis, innate immunity, epithelial-to-mesenchymal transition, cell migration, invasion, metastasis and differentiation. Although XIAP localizes to the cytosolic compartment, XIAP-mediated cellular signaling encompasses mitochondrial and post-mitochondrial levels. Recent findings demonstrate that XIAP also localizes to mitochondria and regulates mitochondria functions. XIAP acts upstream of mitochondrial cytochrome c release and modulates caspase-dependent apoptosis. The new function of XIAP has potential to enhance mitochondrial membrane permeabilization and other cellular functions controlling cytochrome c release. These findings could exploit the overexpression of XIAP in human tumors for therapeutic benefits. Abstract : X-chromosome-linked inhibitor of apoptosis protein (XIAP) inhibits caspases and blocks apoptosis. XIAP can also function as a proapoptotic protein by promoting mitochondrial membrane permeabilization, which could be exploited for therapeutic benefits in cancer.