title: EZH2 phosphorylation regulates Tat-induced HIV-1 transactivation via ROS/Akt signaling pathway.
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.
authors.affiliation: College of Life Science & Bioengineering, Beijing University of Technology, Pingleyuan 100(#), District of Chaoyang, Beijing 100124, China. Electronic address: zhanghs@bjut.edu.cn.
authors.forename: Hong-Sheng
authors.initials: HS
authors.lastname: Zhang
authors.affiliation: College of Life Science & Bioengineering, Beijing University of Technology, Pingleyuan 100(#), District of Chaoyang, Beijing 100124, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Life Science & Bioengineering, Beijing University of Technology, Pingleyuan 100(#), District of Chaoyang, Beijing 100124, China.
authors.forename: Tong-Chao
authors.initials: TC
authors.lastname: Wu
authors.affiliation: College of Life Science & Bioengineering, Beijing University of Technology, Pingleyuan 100(#), District of Chaoyang, Beijing 100124, China.
authors.forename: Guang-Yuan
authors.initials: GY
authors.lastname: Du
authors.affiliation: College of Life Science & Bioengineering, Beijing University of Technology, Pingleyuan 100(#), District of Chaoyang, Beijing 100124, China.
authors.forename: Feng-Juan
authors.initials: FJ
authors.lastname: Zhang
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019943:Amino Acid Substitution; D047369:Chromatin Immunoprecipitation; D000071221:Enhancer of Zeste Homolog 2 Protein; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017930:Genes, Reporter / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D016297:Mutagenesis, Site-Directed; D050505:Mutant Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D063151:Polycomb Repressive Complex 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000819:agonists* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects; D014775:Virus Activation / Q000187:drug effects; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D050505:Mutant Proteins; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; C048460:3-deazaneplanocin; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D000241:Adenosine
keywords: AKT; Enhancer of zeste homolog 2; HIV-1; Reactive oxygen species