کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8473930 | 1550414 | 2016 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Regulation of scleraxis transcriptional activity by serine phosphorylation
ترجمه فارسی عنوان
مقررات فعالیت رونویسی اسکلراکساس با فسفوریلاسیون سریین
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کلمات کلیدی
ECMTGFβbHLHCK2αSMATBBbasic helix-loop-helix - اسلحه پایه حلقه ایpost-translational modification - اصلاح post-translationalα-smooth muscle actin - اکتین عضله آلفا صافTransforming growth factor β - تبدیل فاکتور رشد βTranscription factor - عامل رونویسیPhosphorylation - فسفریلاسیونFibroblast - فیبروبلاستExtracellular matrix - ماتریکس خارج سلولیCasein kinase 2 - کازئین کیناز 2
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
چکیده انگلیسی
Cardiac fibroblasts are the major extracellular matrix producing cells in the heart. Our laboratory was the first to demonstrate that the transcription factor scleraxis induces collagen 1α2 expression in both cardiac fibroblasts and myofibroblasts. Here we identify a novel post-translational mechanism by which scleraxis activity is regulated and determine its effect on transcription of genes targeted by scleraxis. Putative serine phosphorylation sites on scleraxis were revealed by in silico analysis using motif prediction software. Mutation of key serine residues to alanine, which cannot be phosphorylated, significantly attenuated the expression of fibrillar type I collagen and myofibroblast marker genes that are normally induced by scleraxis. Down-regulation of collagen 1α2 expression was due to reduced binding of the non-phosphorylated scleraxis mutant to specific E-box DNA-binding sites within the promoter as determined by chromatin immunoprecipitation in human cardiac myofibroblast cells and by electrophoretic mobility shift assay. This is the first evidence suggesting that scleraxis is phosphorylated under basal conditions. The phosphorylation sequence matched that targeted by Casein Kinase 2, and inhibition of this kinase activity disrupted the ability of scleraxis to modulate the expression of its target genes while also attenuating TGFβ-induced expression of type I collagen and myofibroblast phenotype conversion marker genes. These results demonstrate a novel mechanism for regulation of scleraxis activity, which may prove to be tractable for pharmacologic manipulation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular and Cellular Cardiology - Volume 92, March 2016, Pages 140-148
Journal: Journal of Molecular and Cellular Cardiology - Volume 92, March 2016, Pages 140-148
نویسندگان
Rushita A. Bagchi, Ryan Wang, Fahmida Jahan, Jeffrey T. Wigle, Michael P. Czubryt,