aPKC Phosphorylates p27Xic1, Providing a Mechanistic Link between Apicobasal Polarity and Cell-Cycle Control

作者：Sabherwal Nitin^*; Thuret Raphael; Lea Robert; Stanley Peter; Papalopulu Nancy

来源：Developmental Cell, 2014, 31(5): 559-571.

DOI：10.1016/j.devcel.2014.10.023

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.

• 出版日期2014-12