University of Oulu

Horbach T, Chi TF, Götz C, Sharma S, Juffer AH, Dimova EY, et al. (2014) GSK3β-Dependent Phosphorylation Alters DNA Binding, Transactivity and Half-Life of the Transcription Factor USF2. PLoS ONE 9(9): e107914. doi:10.1371/journal.pone.0107914

GSK3β-dependent phosphorylation alters DNA binding, transactivity and half-life of the transcription factor USF2

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Author: Horbach, Tina1,2; Franklin Chi, Tabughang1; Götz, Claudia3;
Organizations: 1Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Oulu, Finland
2Department of Chemistry, University of Kaiserslautern, Kaiserslautern, Germany
3Medical Biochemistry and Molecular Biology, Saarland University, Homburg, Germany
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.5 MB)
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Language: English
Published: Public Library of Science, 2014
Publish Date: 2017-03-15


The upstream stimulatory factor 2 (USF2) is a regulator of important cellular processes and is supposed to have also a role during tumor development. However, the knowledge about the mechanisms that control the function of USF2 is limited. The data of the current study show that USF2 function is regulated by phosphorylation and identified GSK3β as an USF2-phosphorylating kinase. The phosphorylation sites within USF2 could be mapped to serine 155 and threonine 230. In silico analyses of the 3-dimensional structure revealed that phosphorylation of USF2 by GSK3β converts it to a more open conformation which may influence transactivity, DNA binding and target gene expression. Indeed, experiments with GSK-3β-deficient cells revealed that USF2 transactivity, DNA binding and target gene expression were reduced upon lack of GSK3β. Further, experiments with USF2 variants mimicking GSK3β phosphorylated USF2 in GSK3β-deficient cells showed that phosphorylation of USF2 by GSK3β did not affect cell proliferation but increased cell migration. Together, this study reports a new mechanism by which USF2 may contribute to cancerogenesis.

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Series: PLoS one
ISSN: 1932-6203
ISSN-E: 1932-6203
ISSN-L: 1932-6203
Volume: 9
Issue: 9
Article number: e107914
DOI: 10.1371/journal.pone.0107914
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
Funding: This work was supported by grants from the Wilhelm Sander Foundation (Grant 2008.043.1) to EYD, and from Biocenter Oulu, the Sigrid Juselius Foundation and the Finnish Academy of Science to TK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Dataset Reference: The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper.
Copyright information: Copyright: © 2014 Horbach et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.