Skip to main content
Journal cover image

XIAP Is a copper binding protein deregulated in Wilson's disease and other copper toxicosis disorders.

Publication ,  Journal Article
Mufti, AR; Burstein, E; Csomos, RA; Graf, PCF; Wilkinson, JC; Dick, RD; Challa, M; Son, J-K; Bratton, SB; Su, GL; Brewer, GJ; Jakob, U; Duckett, CS
Published in: Mol Cell
March 17, 2006

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.

Duke Scholars

Published In

Mol Cell

DOI

ISSN

1097-2765

Publication Date

March 17, 2006

Volume

21

Issue

6

Start / End Page

775 / 785

Location

United States

Related Subject Headings

  • X-Linked Inhibitor of Apoptosis Protein
  • Transfection
  • Signal Transduction
  • Protein Conformation
  • Models, Biological
  • Inhibitor of Apoptosis Proteins
  • Humans
  • Hepatolenticular Degeneration
  • Electrophoretic Mobility Shift Assay
  • Developmental Biology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Mufti, A. R., Burstein, E., Csomos, R. A., Graf, P. C. F., Wilkinson, J. C., Dick, R. D., … Duckett, C. S. (2006). XIAP Is a copper binding protein deregulated in Wilson's disease and other copper toxicosis disorders. Mol Cell, 21(6), 775–785. https://doi.org/10.1016/j.molcel.2006.01.033
Mufti, Arjmand R., Ezra Burstein, Rebecca A. Csomos, Paul C. F. Graf, John C. Wilkinson, Robert D. Dick, Madhavi Challa, et al. “XIAP Is a copper binding protein deregulated in Wilson's disease and other copper toxicosis disorders.Mol Cell 21, no. 6 (March 17, 2006): 775–85. https://doi.org/10.1016/j.molcel.2006.01.033.
Mufti AR, Burstein E, Csomos RA, Graf PCF, Wilkinson JC, Dick RD, et al. XIAP Is a copper binding protein deregulated in Wilson's disease and other copper toxicosis disorders. Mol Cell. 2006 Mar 17;21(6):775–85.
Mufti, Arjmand R., et al. “XIAP Is a copper binding protein deregulated in Wilson's disease and other copper toxicosis disorders.Mol Cell, vol. 21, no. 6, Mar. 2006, pp. 775–85. Pubmed, doi:10.1016/j.molcel.2006.01.033.
Mufti AR, Burstein E, Csomos RA, Graf PCF, Wilkinson JC, Dick RD, Challa M, Son J-K, Bratton SB, Su GL, Brewer GJ, Jakob U, Duckett CS. XIAP Is a copper binding protein deregulated in Wilson's disease and other copper toxicosis disorders. Mol Cell. 2006 Mar 17;21(6):775–785.
Journal cover image

Published In

Mol Cell

DOI

ISSN

1097-2765

Publication Date

March 17, 2006

Volume

21

Issue

6

Start / End Page

775 / 785

Location

United States

Related Subject Headings

  • X-Linked Inhibitor of Apoptosis Protein
  • Transfection
  • Signal Transduction
  • Protein Conformation
  • Models, Biological
  • Inhibitor of Apoptosis Proteins
  • Humans
  • Hepatolenticular Degeneration
  • Electrophoretic Mobility Shift Assay
  • Developmental Biology