Essential role of PKCdelta in histone deacetylase inhibitor-induced Epstein-Barr virus reactivation in nasopharyngeal carcinoma cells.
Histone deactylase inhibitors (HDACi) are common chemotherapeutic agents that stimulate Epstein-Barr virus (EBV) reactivation; the detailed mechanism remains obscure. In this study, it is demonstrated that PKCdelta is required for induction of the EBV lytic cycle by HDACi. Inhibition of PKCdelta abrogates HDACi-mediated transcriptional activation of the Zta promoter and downstream lytic gene expression. Nuclear translocation of PKCdelta is observed following HDACi stimulation and its overexpression leads to progression of the EBV lytic cycle. Our study suggests that PKCdelta is a crucial mediator of EBV reactivation and provides a novel insight to study the regulation of the EBV lytic cycle.
Lee
Heng-Huan
HH
Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan, ROC.
Chang
Shih-Shin
SS
Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan, ROC.
Lin
Sue-Jane
SJ
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Chua
Huey-Huey
HH
Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan, ROC.
Tsai
Tze-Jiun
TJ
Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan, ROC.
Tsai
Kevin
K
Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan, ROC.
Lo
You-Chang
YC
Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan, ROC.
Chen
Hong-Chen
HC
Department of Life Science and Graduate Institute of Biomedical Sciences, National Chung Hsing University, 250 Kuo-Kuang Road, Taichung 40227, Taiwan, ROC.
Tsai
Ching-Hwa
CH
Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan, ROC.
D002227:Carbazoles / Q000494:pharmacology; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D020031:Epstein-Barr Virus Infections / Q000821:virology*; D004854:Herpesvirus 4, Human / Q000502:physiology*; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D053652:Nuclear Transfer Techniques; D011401:Promoter Regions, Genetic / Q000235:genetics; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051745:Protein Kinase C-delta / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics; D015533:Transcriptional Activation; D014764:Viral Proteins / Q000235:genetics; D014775:Virus Activation / Q000187:drug effects
C063676:BZLF1 protein, Herpesvirus 4, Human; D002227:Carbazoles; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D007211:Indoles; D008301:Maleimides; D015534:Trans-Activators; D014764:Viral Proteins; C081021:Go 6976; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; C070515:bisindolylmaleimide I