Regulation of S100A10 Gene Expression.

Aleksandra Głowacka,Ewelina Jurewicz,Wiesława Leśniak,Tomasz Wilanowski,Paweł Bieganowski,Anna Filipek

doi:10.3390/biom11070974

Abstract

S100A10, a member of the S100 family of Ca2+-binding proteins, is a widely distributed protein involved in many cellular and extracellular processes. The best recognized role of S100A10 is the regulation, via interaction with annexin A2, of plasminogen conversion to plasmin. Plasmin, together with other proteases, induces degradation of the extracellular matrix (ECM), which is an important step in tumor progression. Additionally, S100A10 interacts with 5-hydroxytryptamine 1B (5-HT1B) receptor, which influences neurotransmitter binding and, through that, depressive symptoms. Taking this into account, it is evident that S100A10 expression in the cell should be under strict control. In this work, we summarize available literature data concerning the physiological stimuli and transcription factors that influence S100A10 expression. We also present our original results showing for the first time regulation of S100A10 expression by grainyhead-like 2 transcription factor (GRHL2). By applying in silico analysis, we have found two highly conserved GRHL2 binding sites in the 1st intron of the gene encoding S100A10 protein. Using chromatin immunoprecipitation (ChIP) and luciferase assays, we have shown that GRHL2 directly binds to these sites and that this DNA region can affect transcription of S100A10.

Highlights

IntroductionPublisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations
In consequence, S100A10 has an effect on degradation of the extracellular matrix (ECM), which is an important step in tumorigenesis/metastasis
Several reports have been published concerning regulation of S100A10 expression. Based on all these data, it is evident that it can be influenced by many different stimuli, which, together with a range of transcription factors, ensure that the S100A10 protein level meets the demands of a given cell

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Is insensitive to changes in Ca2+ concentration Both “EF hand” motifs in S100A10 have amino acid substitutions that allow them to maintain a conformation, which resembles that of other S100 proteins in a Ca2+ -bound form. S100A10 has been verified experimentally, providing relecognate binding sites within the regulatory regions of S100A10 has been verified expervant information on the regulation of. MAPK, PI3K, and JNK cascades in response to BDNF or FGF2 stimulation and constitutes one of the mechanisms of antidepressant response in which S100A10 plays a significant role [16] Another group demonstrated the binding of Sp1, and probably of Sp3, to a GC-box within the −96 to −70 segment of the S100A10 promoter using electrophoretic mobility shift assay (EMSA) [18]. It was revealed that dexametasone-induced S100A10 expression involves glucocorticoid receptor (GR) binding sites in the promoter sequence [22].

Influence of GRHL2 on S100A10 Expression

Results are presented as means

Methods and Figure

Analysis of S100A10 mRNA in RC-124 Cells with Silenced GRHL2 Expression

Results

Conclusions