title: Epstein-Barr Virus nuclear antigen 1 (EBNA1) confers resistance to apoptosis in EBV-positive B-lymphoma cells through up-regulation of survivin.
abstract: Resistance to apoptosis is an important component of the overall mechanism which drives the tumorigenic process. EBV is a ubiquitous human gamma-herpesvirus which preferentially establishes latent infection in viral infected B-lymphocytes. EBNA1 is typically expressed in most forms of EBV-positive malignancies and is important for replication of the latent episome in concert with replication of the host cells. Here, we investigate the effects of EBNA1 on survivin up-regulation in EBV-infected human B-lymphoma cells. We present evidence which demonstrates that EBNA1 forms a complex with Sp1 or Sp1-like proteins bound to their cis-element at the survivin promoter. This enhances the activity of the complex and up-regulates survivin. Knockdown of survivin and EBNA1 showed enhanced apoptosis in infected cells and thus supports a role for EBNA1 in suppressing apoptosis in EBV-infected cells. Here, we suggest that EBV encoded EBNA1 can contribute to the oncogenic process by up-regulating the apoptosis suppressor protein, survivin in EBV-associated B-lymphoma cells.
authors.affiliation: Department of Microbiology and Tumor Virology Program, Abramson Comprehensive Cancer Center, School of Medicine, University of Pennsylvania, 202E Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Lu
authors.forename: Masanao
authors.initials: M
authors.lastname: Murakami
authors.forename: Subhash C
authors.initials: SC
authors.lastname: Verma
authors.forename: Qiliang
authors.initials: Q
authors.lastname: Cai
authors.forename: Sabyasachi
authors.initials: S
authors.lastname: Haldar
authors.forename: Rajeev
authors.initials: R
authors.lastname: Kaul
authors.forename: Mariusz A
authors.initials: MA
authors.lastname: Wasik
authors.forename: Jaap
authors.initials: J
authors.lastname: Middeldorp
authors.forename: Erle S
authors.initials: ES
authors.lastname: Robertson
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D001402:B-Lymphocytes / Q000378:metabolism* / Q000821:virology*; D045744:Cell Line, Tumor; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics / Q000378:metabolism*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D000077022:Survivin; D015533:Transcriptional Activation; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: C107489:BIRC5 protein, human; D019309:Epstein-Barr Virus Nuclear Antigens; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D016329:Sp1 Transcription Factor; D000077022:Survivin; C417029:EBV-encoded nuclear antigen 1