Regulation of the copper chaperone CCS by XIAP-mediated ubiquitination.

Article Details


Brady GF, Galban S, Liu X, Basrur V, Gitlin JD, Elenitoba-Johnson KS, Wilson TE, Duckett CS

Regulation of the copper chaperone CCS by XIAP-mediated ubiquitination.

Mol Cell Biol. 2010 Apr;30(8):1923-36. doi: 10.1128/MCB.00900-09. Epub 2010 Feb 12.

PubMed ID
20154138 [ View in PubMed

In order to balance the cellular requirements for copper with its toxic properties, an elegant set of mechanisms has evolved to regulate and buffer intracellular copper. The X-linked inhibitor of apoptosis (XIAP) protein was recently identified as a copper-binding protein and regulator of copper homeostasis, although the mechanism by which XIAP binds copper in the cytosol is unclear. Here we describe the identification of the copper chaperone for superoxide dismutase (CCS) as a mediator of copper delivery to XIAP in cells. We also find that CCS is a target of the E3 ubiquitin ligase activity of XIAP, although interestingly, ubiquitination of CCS by XIAP was found to lead to enhancement of its chaperone activity toward its physiologic target, superoxide dismutase 1, rather than proteasomal degradation. Collectively, our results reveal novel links among apoptosis, copper metabolism, and redox regulation through the XIAP-CCS complex.

DrugBank Data that Cites this Article

NameUniProt ID
E3 ubiquitin-protein ligase XIAPP98170Details
Copper chaperone for superoxide dismutaseO14618Details