Prolyl isomerase Pin1 and protein kinase HIPK2 cooperate to promote cortical neurogenesis by suppressing groucho/TLE: Hes1-mediated inhibition of neuronal differentiation

R. Ciarapica, L. Methot, Y. Tang, R. Lo, R. Dali, M. Buscarlet, F. Locatelli, G. Del Sal, R. Rota, S. Stifani

Research output: Contribution to journalArticle

Abstract

The Groucho/transducin-like Enhancer of split 1 (Gro/TLE1):Hes1 transcriptional repression complex acts in cerebral cortical neural progenitor cells to inhibit neuronal differentiation. The molecular mechanisms that regulate the anti-neurogenic function of the Gro/TLE1:Hes1 complex during cortical neurogenesis remain to be defined. Here we show that prolyl isomerase Pin1 (peptidyl-prolyl cis-trans isomerase NIMA-interacting 1) and homeodomain-interacting protein kinase 2 (HIPK2) are expressed in cortical neural progenitor cells and form a complex that interacts with the Gro/TLE1:Hes1 complex. This association depends on the enzymatic activities of both HIPK2 and Pin1, as well as on the association of Gro/TLE1 with Hes1, but is independent of the previously described Hes1-activated phosphorylation of Gro/TLE1. Interaction with the Pin1:HIPK2 complex results in Gro/TLE1 hyperphosphorylation and weakens both the transcriptional repression activity and the anti-neurogenic function of the Gro/TLE1:Hes1 complex. These results provide evidence that HIPK2 and Pin1 work together to promote cortical neurogenesis, at least in part, by suppressing Gro/TLE1:Hes1-mediated inhibition of neuronal differentiation.

Original languageEnglish
Pages (from-to)321-332
Number of pages12
JournalCell Death and Differentiation
Volume21
Issue number2
DOIs
Publication statusPublished - Feb 2014

Keywords

  • cerebral cortex
  • Groucho/transducin-like Enhancer of split
  • Hes1
  • HIPK2
  • neuronal differentiation
  • Pin1

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Medicine(all)

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