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

Hong-Sheng Zhang; Yang Liu; Tong-Chao Wu; Guang-Yuan Du; Feng-Juan Zhang

doi:10.1016/j.febslet.2015.11.033

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.

Authors

Hong-Sheng Zhang¹, Yang Liu², Tong-Chao Wu², Guang-Yuan Du², Feng-Juan Zhang²

Affiliations

¹ College of Life Science & Bioengineering, Beijing University of Technology, Pingleyuan 100(#), District of Chaoyang, Beijing 100124, China. Electronic address: [email protected].
² College of Life Science & Bioengineering, Beijing University of Technology, Pingleyuan 100(#), District of Chaoyang, Beijing 100124, China.

PMID: 26632198
DOI: 10.1016/j.febslet.2015.11.033

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