Nuclear Localization of Diacylglycerol Kinase Alpha in K562 Cells Is Involved in Cell Cycle Progression

J Cell Physiol. 2017 Sep;232(9):2550-2557. doi: 10.1002/jcp.25642. Epub 2017 Apr 10.

Abstract

Phosphatidylinositol (PI) signaling is an essential regulator of cell motility and proliferation. A portion of PI metabolism and signaling takes place in the nuclear compartment of eukaryotic cells, where an array of kinases and phosphatases localize and modulate PI. Among these, Diacylglycerol Kinases (DGKs) are a class of phosphotransferases that phosphorylate diacylglycerol and induce the synthesis of phosphatidic acid. Nuclear DGKalpha modulates cell cycle progression, and its activity or expression can lead to changes in the phosphorylated status of the Retinoblastoma protein, thus, impairing G1/S transition and, subsequently, inducing cell cycle arrest, which is often uncoupled with apoptosis or autophagy induction. Here we report for the first time not only that the DGKalpha isoform is highly expressed in the nuclei of human erythroleukemia cell line K562, but also that its nuclear activity drives K562 cells through the G1/S transition during cell cycle progression. J. Cell. Physiol. 232: 2550-2557, 2017. © 2016 Wiley Periodicals, Inc.

MeSH terms

  • Cell Nucleus / drug effects
  • Cell Nucleus / enzymology*
  • Cell Nucleus / pathology
  • Cell Proliferation* / drug effects
  • Diacylglycerol Kinase / antagonists & inhibitors
  • Diacylglycerol Kinase / genetics
  • Diacylglycerol Kinase / metabolism*
  • Dose-Response Relationship, Drug
  • G1 Phase Cell Cycle Checkpoints* / drug effects
  • Humans
  • Isoenzymes
  • K562 Cells
  • Leukemia, Erythroblastic, Acute / enzymology*
  • Leukemia, Erythroblastic, Acute / genetics
  • Leukemia, Erythroblastic, Acute / pathology
  • Phosphorylation
  • Protein Kinase Inhibitors / pharmacology
  • RNA Interference
  • Retinoblastoma Protein / metabolism
  • Signal Transduction
  • Time Factors
  • Transfection

Substances

  • Isoenzymes
  • Protein Kinase Inhibitors
  • Retinoblastoma Protein
  • Diacylglycerol Kinase