aPKC phosphorylates p27Xic1, providing a mechanistic link between apicobasal polarity and cell-cycle control

Dev Cell. 2014 Dec 8;31(5):559-71. doi: 10.1016/j.devcel.2014.10.023.

Abstract

During the development of the nervous system, apicobasally polarized stem cells are characterized by a shorter cell cycle than nonpolar progenitors, leading to a lower differentiation potential of these cells. However, how polarization might be directly linked to the kinetics of the cell cycle is not understood. Here, we report that apicobasally polarized neuroepithelial cells in Xenopus laevis have a shorter cell cycle than nonpolar progenitors, consistent with mammalian systems. We show that the apically localized serine/threonine kinase aPKC directly phosphorylates an N-terminal site of the cell-cycle inhibitor p27Xic1 and reduces its ability to inhibit the cyclin-dependent kinase 2 (Cdk2), leading to shortening of G1 and S phases. Overexpression of activated aPKC blocks the neuronal differentiation-promoting activity of p27Xic1. These findings provide a direct mechanistic link between apicobasal polarity and the cell cycle, which may explain how proliferation is favored over differentiation in polarized neural stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Checkpoints / physiology*
  • Cell Differentiation / physiology
  • Cell Division / physiology
  • Cell Polarity / physiology*
  • Cyclin-Dependent Kinase 2 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism*
  • Phosphorylation
  • Protein Kinase C / metabolism*
  • Protein Serine-Threonine Kinases / metabolism
  • Xenopus Proteins / metabolism*
  • Xenopus laevis

Substances

  • Xenopus Proteins
  • Xicl protein, Xenopus
  • Cyclin-Dependent Kinase Inhibitor p27
  • Protein Serine-Threonine Kinases
  • Protein Kinase C
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2