NOK mediates glycolysis and nuclear PDC associated histone acetylation

Front Biosci (Landmark Ed). 2017 Jun 1;22(10):1792-1804. doi: 10.2741/4572.

Abstract

NOK is a potent oncogene that can transform normal cells to cancer cells. We hypothesized that NOK might impact cancer cell metabolism and histone acetylation. We show that NOK localizes in the mitochondria, and while it minimally impacts tricarboxylic acid (TCA) cycle, it markedly inhibits the process of electron transport and oxidative phosphorylation processes and dramatically enhances aerobic glycolysis in cancer cells. NOK promotes the mitochondrial-nuclear translocation of pyruvate dehydrogenase complex (PDC), and enhances histone acetylation in the nucleus. Together, these findings show that NOK mediates glycolysis and nuclear PDC associated histone acetylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Active Transport, Cell Nucleus
  • Animals
  • Blotting, Western
  • Cell Line
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Gene Expression
  • Glycolysis*
  • HEK293 Cells
  • Histones / metabolism*
  • Humans
  • Mice
  • Microscopy, Confocal
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • NIH 3T3 Cells
  • Pyruvate Dehydrogenase Complex / genetics
  • Pyruvate Dehydrogenase Complex / metabolism*
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Histones
  • Pyruvate Dehydrogenase Complex
  • Receptor Protein-Tyrosine Kinases
  • STYK1 protein, human