Regulation of scleraxis transcriptional activity by serine phosphorylation

Journal of Molecular and Cellular Cardiology
Rushita A BagchiMichael P Czubryt

Abstract

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...Continue Reading

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Citations

Mar 12, 2016·Journal of Molecular and Cellular Cardiology·Joy Lincoln
Oct 21, 2016·Cell and Tissue Research·Rushita A BagchiMichael P Czubryt
Mar 9, 2017·Canadian Journal of Physiology and Pharmacology·Danah Al Hattab, Michael P Czubryt
Jun 29, 2018·European Journal of Immunology·Guobao ChenDaniela Čiháková
Nov 6, 2018·Canadian Journal of Physiology and Pharmacology·Ryan WangRushita A Bagchi
Aug 21, 2019·Journal of Cardiovascular Development and Disease·Michael P Czubryt
Feb 23, 2020·Nature Reviews. Rheumatology·Eric GraceyDirk Elewaut
Feb 7, 2020·Canadian Journal of Physiology and Pharmacology·Antonia ZhuDavinder S Jassal

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