期刊
EMBO JOURNAL
卷 23, 期 1, 页码 244-254出版社
WILEY
DOI: 10.1038/sj.emboj.7600031
关键词
copper; MURR1; ubiquitin; XIAP
资金
- NCI NIH HHS [T32 CA09676, T32 CA009676] Funding Source: Medline
- NIDDK NIH HHS [P30 DK034933, 5P30 DK34933-18] Funding Source: Medline
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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