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Title: | Differential transcriptional and post-translational transcription factor 7-like regulation among nondiabetic individuals and type 2 diabetic patients. |
Author: | Pradas-Juni, Marta Nicod, Nathalie Fernández-Rebollo, Eduardo Gomis, Ramon, 1946- |
Keywords: | Diabetis Expressió gènica Biosíntesi Proteïnes Factors de transcripció Genètica molecular Diabetes Gene expression Biosynthesis Proteins Transcription factors Molecular genetics |
Issue Date: | 24-Jul-2014 |
Publisher: | Endocrine Society |
Abstract: | Human genetic studies have revealed that the T minor allele of single nucleotide polymorphism rs7903146 in the transcription factor 7-like 2 (TCF7L2) gene is strongly associated with an increased risk of diabetes by 30%-40%. Molecular and clinical studies are of great importance for understanding how this unique variation in TCF7L2 influences type 2 diabetes (T2D) onset and progression. At the molecular level, some studies have been performed in diabetic mice and pancreatic islets from healthy human donors. Whereas TCF7L2 mRNA levels are up-regulated in islets, protein levels are down-regulated. We performed studies on TCF7L2 splicing, mRNA expression, and protein levels in immortalized human lymphocytes from nondiabetic individuals and T2D patients carrying the C/C or the at-risk T/T genotype. Our results show differential expression of TCF7L2 splice variants between nondiabetic and T2D patients carrying the at-risk genotype, as well as differences in protein levels. Therefore, we investigated the regulation of splice variants, and our results propose that splicing of exon 4 is under control of the serine-arginine-rich factor transformer 2 β (TRA2B). Finally, we studied the endoplasmic reticulum stress pathways, looking for a posttranslational explanation. We saw a shift in the activation of these pathways between nondiabetic individuals and T2D patients carrying the at-risk genotype. These results suggest that, in human immortalized lymphocytes carrying the at-risk T/T genotype, first the differential expression of TCF7L2 splice variants implies a regulation, at least for exon 4, by TRA2B and second, the differential protein levels between both T/T carriers point to a different activation of endoplasmic reticulum stress pathways. |
Note: | Reproducció del document publicat a: https://doi.org/10.1210/me.2014-1065 |
It is part of: | Molecular Endocrinology, 2014, vol. 28, num. 9, p. 1558-1570 |
URI: | http://hdl.handle.net/2445/120315 |
Related resource: | https://doi.org/10.1210/me.2014-1065 |
ISSN: | 0888-8809 |
Appears in Collections: | Articles publicats en revistes (Medicina) Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) |
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