Cyclin-dependent kinasedependent phosphorylation of Sox2 at serine 39 regulates neurogenesis

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Shuhui Lim - , Agency for Science, Technology and Research, Singapore, Nanyang Technological University, Merck & Co., Inc (Autor:in)
  • Akshay Bhinge - , Agency for Science, Technology and Research, Singapore, University of Exeter (Autor:in)
  • Sara Bragado Alonso - , Technische Universität Dresden (Autor:in)
  • Irene Aksoy - , Agency for Science, Technology and Research, Singapore, Universite Claude Bernard Lyon 1 (Autor:in)
  • Julieta Aprea - , Center for Regenerative Therapies Dresden (CRTD) (Autor:in)
  • Chit Fang Cheok - , FIRC Institute of Molecular Oncology, National University of Singapore (Autor:in)
  • Federico Calegari - , Center for Regenerative Therapies Dresden (CRTD), Professur für Proliferation von neuralen Stammzellen von Säugetieren (Autor:in)
  • Lawrence W. Stanton - , Agency for Science, Technology and Research, Singapore (Autor:in)
  • Philipp Kaldis - , Agency for Science, Technology and Research, Singapore, National University of Singapore (Autor:in)

Abstract

Sox2 is known to be important for neuron formation, but the precise mechanism through which it activates a neurogenic program and how this differs from its well-established function in self-renewal of stem cells remain elusive. In this study, we identified a highly conserved cyclin-dependent kinase (Cdk) phosphorylation site on serine 39 (S39) in Sox2. In neural stem cells (NSCs), phosphorylation of S39 enhances the ability of Sox2 to negatively regulate neuronal differentiation, while loss of phosphorylation is necessary for chromatin retention of a truncated form of Sox2 generated during neurogenesis. We further demonstrated that nonphosphorylated cleaved Sox2 specifically induces the expression of proneural genes and promotes neurogenic commitment in vivo. Our present study sheds light on how the level of Cdk kinase activity directly regulates Sox2 to tip the balance between self-renewal and differentiation in NSCs.

Details

OriginalspracheEnglisch
Aufsatznummere00201-17
FachzeitschriftMolecular and cellular biology
Jahrgang37
Ausgabenummer16
PublikationsstatusVeröffentlicht - 1 Aug. 2017
Peer-Review-StatusJa

Externe IDs

PubMed 28584195
ORCID /0000-0002-8749-7878/work/142251292

Schlagworte

ASJC Scopus Sachgebiete

Schlagwörter

  • Cdks, Cell cycle regulation, Cyclin-dependent kinases, Differentiation, Neural stem cells, Self-renewal, Sox2

Bibliotheksschlagworte