کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2188696 1096182 2006 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Structural Determinants Involved in the Regulation of CXCL14/BRAK Expression by the 26 S Proteasome
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Structural Determinants Involved in the Regulation of CXCL14/BRAK Expression by the 26 S Proteasome
چکیده انگلیسی

The chemokine CXCL14/BRAK participates in immune surveillance by recruiting dendritic cells. CXCL14 gene expression is altered in a number of cancers, but protein expression levels have not been investigated. Here we report that CXCL14 protein can be expressed in primary epithelial cells; however, in several immortalized and cancer cell lines this protein is targeted for polyubiquitylation and proteasomal degradation. We determined the NMR structure of CXCL14 to identify motifs controlling its expression. CXCL14 adopts the canonical chemokine tertiary fold but contains a unique five amino acid insertion (41VSRYR45) relative to other CXC chemokines. Deletion or substitution of key residues within this insertion prevented proteasomal degradation. Furthermore, we defined a 15 amino acid fragment of CXCL14 that is sufficient to induce proteasomal degradation. This study elucidates a post-translational mechanism for the loss of CXCL14 in cancer and a novel mode of chemokine regulation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular Biology - Volume 363, Issue 4, 3 November 2006, Pages 813–822
نویسندگان
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