title: Epstein-Barr virus nuclear antigen 3C stabilizes Gemin3 to block p53-mediated apoptosis.
abstract: The Epstein-Barr nuclear antigen 3C (EBNA3C), one of the essential latent antigens for Epstein-Barr virus (EBV)-induced immortalization of primary human B lymphocytes in vitro, has been implicated in regulating cell proliferation and anti-apoptosis via interaction with several cellular and viral factors. Gemin3 (also named DDX20 or DP103) is a member of DEAD RNA helicase family which exhibits diverse cellular functions including DNA transcription, recombination and repair, and RNA metabolism. Gemin3 was initially identified as a binding partner to EBNA2 and EBNA3C. However, the mechanism by which EBNA3C regulates Gemin3 function remains unclear. Here, we report that EBNA3C directly interacts with Gemin3 through its C-terminal domains. This interaction results in increased stability of Gemin3 and its accumulation in both B lymphoma cells and EBV transformed lymphoblastoid cell lines (LCLs). Moreover, EBNA3C promotes formation of a complex with p53 and Gemin3 which blocks the DNA-binding affinity of p53. Small hairpin RNA based knockdown of Gemin3 in B lymphoma or LCL cells remarkably attenuates the ability of EBNA3C to inhibit the transcription activity of p53 on its downstream genes p21 and Bax, as well as apoptosis. These findings provide the first evidence that Gemin3 may be a common target of oncogenic viruses for driving cell proliferation and anti-apoptotic activities.
authors.affiliation: Department of Microbiology and the Tumor Virology Program, Abramson Comprehensive Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Qiliang
authors.initials: Q
authors.lastname: Cai
authors.forename: Yi
authors.initials: Y
authors.lastname: Guo
authors.forename: Bingyi
authors.initials: B
authors.lastname: Xiao
authors.forename: Shuvomoy
authors.initials: S
authors.lastname: Banerjee
authors.forename: Abhik
authors.initials: A
authors.lastname: Saha
authors.forename: Jie
authors.initials: J
authors.lastname: Lu
authors.forename: Tina
authors.initials: T
authors.lastname: Glisovic
authors.forename: Erle S
authors.initials: ES
authors.lastname: Robertson
mesh_terms: D000956:Antigens, Viral / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology*; D001402:B-Lymphocytes / Q000378:metabolism / Q000821:virology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D055541:DEAD Box Protein 20 / Q000235:genetics / Q000378:metabolism*; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000378:metabolism*; D019309:Epstein-Barr Virus Nuclear Antigens; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D055785:Gene Knockdown Techniques; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000956:Antigens, Viral; C498774:EBNA-3C, epstein-barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D055541:DEAD Box Protein 20