@article{f8ee443d6c904cf7ad6baf069f64e9be,
title = "XIAP is a copper binding protein deregulated in Wilson's disease and other copper toxicosis disorders",
abstract = "X-linked inhibitor of apoptosis (XIAP), known primarily for its caspase inhibitory properties, has recently been shown to interact with and regulate the levels of COMMD1, a protein associated with a form of canine copper toxicosis. Here, we describe a role for XIAP in copper metabolism. We find that XIAP levels are greatly reduced by intracellular copper accumulation in Wilson's disease and other copper toxicosis disorders and in cells cultured under high copper conditions. Elevated copper levels result in a profound, reversible conformational change in XIAP due to the direct binding of copper to XIAP, which accelerates its degradation and significantly decreases its ability to inhibit caspase-3. This results in a lowering of the apoptotic threshold, sensitizing the cell to apoptosis. These data provide an unsuspected link between copper homeostasis and the regulation of cell death through XIAP and may contribute to the pathophysiology of copper toxicosis disorders.",
author = "Mufti, {Arjmand R.} and Ezra Burstein and Csomos, {Rebecca A.} and Graf, {Paul C.F.} and Wilkinson, {John C.} and Dick, {Robert D.} and Madhavi Challa and Son, {Jae Kyoung} and Bratton, {Shawn B.} and Su, {Grace L.} and Brewer, {George J.} and Ursula Jakob and Duckett, {Colin S.}",
note = "Funding Information: We thank Drs. Cisca Wijmenga, Leo Klomp, and Casey Wright for their insightful suggestions, Dr. Hellan Kang for helping with hepatocyte isolation from toxic milk mice, Amanda Wilkinson for technical assistance, and Drs. P. Liston and R. Korneluk for the pcDNA3-Myc 6 -cIAP-2 and NAIP plasmids. This work was supported in part by the University of Michigan Biological Scholars Program, Department of Defense IDEA Award PC040215, and National Institutes of Health Grant GM067827 to C.S.D.; by an American Gastroenterological Association Research Scholar Award, a Merit Review Entry Program Award, and a Veterans Education and Research Association of Michigan Award to E.B.; by a Department of Defense Prostate Cancer Research Program Postdoctoral Training Award PC040393 to J.C.W; by US Food and Drug Administration grants FD-R-002153 and FD-R-002132 and a General Clinical Research Center grant M01-RR00042 to G.J.B.; and by an American Cancer Society grant RSG-05-029-01-CCG to S.B.B. ",
year = "2006",
month = mar,
day = "17",
doi = "10.1016/j.molcel.2006.01.033",
language = "English (US)",
volume = "21",
pages = "775--785",
journal = "Molecular cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "6",
}