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

Tina Horbach1, Tabughang Franklin Chi2, Claudia Götz3

  • 1Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Oulu, Finland; Department of Chemistry, University of Kaiserslautern, Kaiserslautern, Germany.

Plos One
|September 20, 2014
PubMed

Insights

Upstream stimulatory factor 2 (USF2) function, crucial in cell processes, is regulated by GSK3β-mediated phosphorylation. This phosphorylation impacts USF2

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Cancer Research

Background:

  • Upstream stimulatory factor 2 (USF2) regulates critical cellular processes.
  • The precise mechanisms governing USF2 function, particularly in tumor development, remain incompletely understood.
  • Understanding USF2 regulation is key to elucidating its role in cancerogenesis.

Purpose of the Study:

  • To investigate the regulatory mechanisms controlling USF2 function.
  • To identify kinases that phosphorylate USF2.
  • To elucidate the functional consequences of USF2 phosphorylation in cellular processes relevant to cancer.

Main Methods:

  • In silico analysis of USF2 3D structure.
  • Identification of USF2 phosphorylation sites (Serine 155, Threonine 230).
  • Biochemical assays using GSK3β-deficient cells and USF2 variants.

Main Results:

  • Glycogen synthase kinase 3 beta (GSK3β) was identified as a kinase that phosphorylates USF2 at Serine 155 and Threonine 230.
  • Phosphorylation by GSK3β induces a more open conformation of USF2, potentially affecting its DNA binding and transactivity.
  • GSK3β deficiency reduced USF2 transactivity, DNA binding, and target gene expression.
  • Phosphorylation of USF2 by GSK3β did not affect cell proliferation but enhanced cell migration.

Conclusions:

  • USF2 function is regulated by phosphorylation, with GSK3β identified as a key phosphorylating kinase.
  • GSK3β-mediated phosphorylation of USF2 influences its conformation and activity, impacting DNA binding and gene expression.
  • This regulatory mechanism highlights a novel pathway through which USF2 may contribute to cancer development, specifically by promoting cell migration.

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