Insulin/IGF1-PI3K-dependent nucleolar localization of a glycolytic enzyme--phosphoglycerate mutase 2, is necessary for proper structure of nucleolus and RNA synthesis

Oncotarget. 2015 Jul 10;6(19):17237-50. doi: 10.18632/oncotarget.4044.

Abstract

Phosphoglycerate mutase (PGAM), a conserved, glycolytic enzyme has been found in nucleoli of cancer cells. Here, we present evidence that accumulation of PGAM in the nucleolus is a universal phenomenon concerning not only neoplastically transformed but also non-malignant cells. Nucleolar localization of the enzyme is dependent on the presence of the PGAM2 (muscle) subunit and is regulated by insulin/IGF-1-PI3K signaling pathway as well as drugs influencing ribosomal biogenesis. We document that PGAM interacts with several 40S and 60S ribosomal proteins and that silencing of PGAM2 expression results in disturbance of nucleolar structure, inhibition of RNA synthesis and decrease of the mitotic index of squamous cell carcinoma cells. We conclude that presence of PGAM in the nucleolus is a prerequisite for synthesis and initial assembly of new pre-ribosome subunits.

Keywords: PGAM2; multifunctional enzyme; rRNA; ribosome assembly; squamous cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Nucleolus / metabolism*
  • Female
  • Fluorescent Antibody Technique
  • Gene Knockdown Techniques
  • Humans
  • Insulin / metabolism
  • Insulin-Like Growth Factor I / metabolism
  • Mass Spectrometry
  • Mice
  • Microscopy, Confocal
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoglycerate Mutase / metabolism*
  • Transcription, Genetic / physiology*
  • Transfection

Substances

  • Insulin
  • Insulin-Like Growth Factor I
  • Phosphatidylinositol 3-Kinases
  • Phosphoglycerate Mutase