کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1927110 1536499 2007 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
XIAP: Cell death regulation meets copper homeostasis
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
XIAP: Cell death regulation meets copper homeostasis
چکیده انگلیسی

X-linked inhibitor of apoptosis (XIAP), traditionally known as an anti-apoptotic protein, has recently been shown to be involved in copper homeostasis. XIAP promotes the ubiquitination and degradation of COMMD1, a protein that promotes the efflux of copper from the cell. Through its effects on COMMD1, XIAP can regulate copper export from the cell and potentially represents an additional intracellular sensor for copper levels. XIAP binds copper directly and undergoes a substantial conformational change in the copper-bound state. This in turn destabilizes XIAP, resulting in lowered steady-state levels of the protein. Furthermore, copper-bound XIAP is unable to inhibit caspases and cells that express this form of the protein exhibit increased rates of cell death in response to apoptotic stimuli. These events take place in the setting of excess intracellular copper accumulation as seen in copper toxicosis disorders such as Wilson’s disease and establish a new relationship between copper levels and the regulation of cell death via XIAP. These findings raise important questions about the role of XIAP in the development of copper toxicosis disorders and may point to XIAP as a potential therapeutic target in these disease states.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Archives of Biochemistry and Biophysics - Volume 463, Issue 2, 15 July 2007, Pages 168–174
نویسندگان
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