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A novel role for XIAP in copper homeostasis through regulation of MURR1.

Publication ,  Journal Article
Burstein, E; Ganesh, L; Dick, RD; van De Sluis, B; Wilkinson, JC; Klomp, LWJ; Wijmenga, C; Brewer, GJ; Nabel, GJ; Duckett, CS
Published in: EMBO J
January 14, 2004

XIAP is a potent suppressor of apoptosis that directly inhibits specific members of the caspase family of cysteine proteases. Here we demonstrate a novel role for XIAP in the control of intracellular copper levels. XIAP was found to interact with MURR1, a factor recently implicated in copper homeostasis. XIAP binds to MURR1 in a manner that is distinct from that utilized by XIAP to bind caspases, and consistent with this, MURR1 did not affect the antiapoptotic properties of XIAP. However, cells and tissues derived from Xiap-deficient mice were found to contain reduced copper levels, while suppression of MURR1 resulted in increased intracellular copper in cultured cells. Consistent with these opposing effects, XIAP was observed to negatively regulate MURR1 protein levels by the formation of K48 polyubiquitin chains on MURR1 that promote its degradation. These findings represent the first described phenotypic alteration in Xiap-deficient mice and demonstrate that XIAP can function through MURR1 to regulate copper homeostasis.

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Published In

EMBO J

DOI

ISSN

0261-4189

Publication Date

January 14, 2004

Volume

23

Issue

1

Start / End Page

244 / 254

Location

England

Related Subject Headings

  • X-Linked Inhibitor of Apoptosis Protein
  • Ubiquitin
  • Two-Hybrid System Techniques
  • Recombinant Fusion Proteins
  • RNA, Small Interfering
  • RNA Interference
  • Proteins
  • Protein Biosynthesis
  • Precipitin Tests
  • Point Mutation
 

Citation

APA
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ICMJE
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Burstein, E., Ganesh, L., Dick, R. D., van De Sluis, B., Wilkinson, J. C., Klomp, L. W. J., … Duckett, C. S. (2004). A novel role for XIAP in copper homeostasis through regulation of MURR1. EMBO J, 23(1), 244–254. https://doi.org/10.1038/sj.emboj.7600031
Burstein, Ezra, Lakshmanan Ganesh, Robert D. Dick, Bart van De Sluis, John C. Wilkinson, Leo W. J. Klomp, Cisca Wijmenga, George J. Brewer, Gary J. Nabel, and Colin S. Duckett. “A novel role for XIAP in copper homeostasis through regulation of MURR1.EMBO J 23, no. 1 (January 14, 2004): 244–54. https://doi.org/10.1038/sj.emboj.7600031.
Burstein E, Ganesh L, Dick RD, van De Sluis B, Wilkinson JC, Klomp LWJ, et al. A novel role for XIAP in copper homeostasis through regulation of MURR1. EMBO J. 2004 Jan 14;23(1):244–54.
Burstein, Ezra, et al. “A novel role for XIAP in copper homeostasis through regulation of MURR1.EMBO J, vol. 23, no. 1, Jan. 2004, pp. 244–54. Pubmed, doi:10.1038/sj.emboj.7600031.
Burstein E, Ganesh L, Dick RD, van De Sluis B, Wilkinson JC, Klomp LWJ, Wijmenga C, Brewer GJ, Nabel GJ, Duckett CS. A novel role for XIAP in copper homeostasis through regulation of MURR1. EMBO J. 2004 Jan 14;23(1):244–254.

Published In

EMBO J

DOI

ISSN

0261-4189

Publication Date

January 14, 2004

Volume

23

Issue

1

Start / End Page

244 / 254

Location

England

Related Subject Headings

  • X-Linked Inhibitor of Apoptosis Protein
  • Ubiquitin
  • Two-Hybrid System Techniques
  • Recombinant Fusion Proteins
  • RNA, Small Interfering
  • RNA Interference
  • Proteins
  • Protein Biosynthesis
  • Precipitin Tests
  • Point Mutation