EZH2 phosphorylation regulates Tat-induced HIV-1 transactivation via ROS/Akt signaling pathway

FEBS Lett. 2015 Dec 21;589(24 Pt B):4106-11. doi: 10.1016/j.febslet.2015.11.033. Epub 2015 Nov 26.

Abstract

EZH2 plays a major role in HIV-1 latency, however, the molecular linkage between Tat-induced HIV-1 transactivation and EZH2 activity is not fully understood. It was shown Tat induced HIV-1 transactivation through inhibiting EZH2 activity. Tat decreased the levels of H3K27me3 and EZH2 occupy at the long terminal repeat (LTR) of HIV-1. We further showed for the first time that transfected with Tat construct resulted in an increase in phosphorylated EZH2 (p-EZH2), mediated by active Akt. ROS/Akt-dependent p-EZH2 was correlated with Tat-induced transactivation. Our study reveals that novel mechanisms allow Tat-induced HIV-1 transactivation by ROS/Akt-dependent downregulating the EZH2 epigenetic silencing machinery.

Keywords: AKT; Enhancer of zeste homolog 2; HIV-1; Reactive oxygen species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives
  • Adenosine / pharmacology
  • Amino Acid Substitution
  • Chromatin Immunoprecipitation
  • Enhancer of Zeste Homolog 2 Protein
  • Enzyme Inhibitors / pharmacology
  • Genes, Reporter / drug effects
  • HIV-1 / drug effects
  • HIV-1 / enzymology
  • HIV-1 / physiology*
  • HeLa Cells
  • Humans
  • Mutagenesis, Site-Directed
  • Mutant Proteins / antagonists & inhibitors
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism
  • Phosphorylation / drug effects
  • Polycomb Repressive Complex 2 / antagonists & inhibitors
  • Polycomb Repressive Complex 2 / genetics
  • Polycomb Repressive Complex 2 / metabolism*
  • Protein Processing, Post-Translational* / drug effects
  • Protein Transport / drug effects
  • Proto-Oncogene Proteins c-akt / agonists*
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA Interference
  • Reactive Oxygen Species / agonists*
  • Reactive Oxygen Species / metabolism
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction* / drug effects
  • Transcriptional Activation / drug effects
  • Virus Activation / drug effects
  • tat Gene Products, Human Immunodeficiency Virus / agonists*
  • tat Gene Products, Human Immunodeficiency Virus / antagonists & inhibitors
  • tat Gene Products, Human Immunodeficiency Virus / genetics
  • tat Gene Products, Human Immunodeficiency Virus / metabolism

Substances

  • Enzyme Inhibitors
  • Mutant Proteins
  • Reactive Oxygen Species
  • Recombinant Fusion Proteins
  • tat Gene Products, Human Immunodeficiency Virus
  • 3-deazaneplanocin
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Polycomb Repressive Complex 2
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt
  • Adenosine