PTEN regulates PLK1 and controls chromosomal stability during cell division. Academic Article uri icon

Overview

abstract

  • PTEN functions as a guardian of the genome through multiple mechanisms. We have previously established that PTEN maintains the structural integrity of chromosomes. In this report, we demonstrate a fundamental role of PTEN in controlling chromosome inheritance to prevent gross genomic alterations. Disruption of PTEN or depletion of PTEN protein phosphatase activity causes abnormal chromosome content, manifested by enlarged or polyploid nuclei. We further identify polo-like kinase 1 (PLK1) as a substrate of PTEN phosphatase. PTEN can physically associate with PLK1 and reduce PLK1 phosphorylation in a phosphatase-dependent manner. We show that PTEN deficiency leads to PLK1 phosphorylation and that a phospho-mimicking PLK1 mutant causes polyploidy, imitating functional deficiency of PTEN phosphatase. Inhibition of PLK1 activity or overexpression of a non-phosphorylatable PLK1 mutant reduces the polyploid cell population. These data reveal a new mechanism by which PTEN controls genomic stability during cell division.

publication date

  • July 11, 2016

Research

keywords

  • Cell Cycle Proteins
  • Cell Division
  • Chromosomal Instability
  • PTEN Phosphohydrolase
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins

Identity

PubMed Central ID

  • PMC5026806

Scopus Document Identifier

  • 84980357133

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2008.03.025

PubMed ID

  • 27398835

Additional Document Info

volume

  • 15

issue

  • 18