title: A potential role of X-linked inhibitor of apoptosis protein in mitochondrial membrane permeabilization and its implication in cancer therapy.
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.
authors.affiliation: Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Chaudhary
authors.affiliation: Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
authors.forename: Neelu
authors.initials: N
authors.lastname: Yadav
authors.affiliation: Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
authors.forename: Tariq A
authors.initials: TA
authors.lastname: Bhat
authors.affiliation: Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
authors.forename: Jordan
authors.initials: J
authors.lastname: O'Malley
authors.affiliation: Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
authors.forename: Dhyan
authors.initials: D
authors.lastname: Chandra
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002463:Cell Membrane Permeability / Q000502:physiology; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism*
chemical_list: D051636:X-Linked Inhibitor of Apoptosis Protein; D045304:Cytochromes c