title: Bmi-1 is induced by the Epstein-Barr virus oncogene LMP1 and regulates the expression of viral target genes in Hodgkin lymphoma cells.
abstract: Polycomb group (PcG) proteins are chromatin modifiers that are necessary for the maintenance and renewal of embryonic and adult stem cells. However, overexpression of the PcG protein, Bmi-1, causes lymphoma in transgenic mice. We show that Bmi-1 is up-regulated in Hodgkin lymphoma (HL) cells by the Epstein-Barr virus (EBV) oncogene latent membrane protein-1 (LMP1) and that this up-regulation is mediated by NF-kappaB signaling. We also show that Bmi-1 is up-regulated by NF-kappaB in EBV-negative HL cells. Down-regulation of LMP1 and Bmi-1 decreased the survival of HL cells, suggesting that Bmi-1 may mediate the prosurvival effects of LMP1-induced NF-kappaB signaling in HL cells. Transcriptional targets of Bmi-1 were identified after its knockdown in an HL cell line. We show here that Bmi-1 and LMP1 down-regulate the ataxia telangiectasia-mutated (ATM) tumor suppressor and conclude that Bmi-1 contributes to LMP1-induced oncogenesis in HL.
authors.affiliation: Cancer Research UK Institute for Cancer Studies, The Medical School, University of Birmingham, Edgbaston, United Kingdom.
authors.forename: Amanda
authors.initials: A
authors.lastname: Dutton
authors.forename: Ciaran B
authors.initials: CB
authors.lastname: Woodman
authors.forename: Marilyn B
authors.initials: MB
authors.lastname: Chukwuma
authors.forename: James I K
authors.initials: JI
authors.lastname: Last
authors.forename: Wenbin
authors.initials: W
authors.lastname: Wei
authors.forename: Martina
authors.initials: M
authors.lastname: Vockerodt
authors.forename: Karl R N
authors.initials: KR
authors.lastname: Baumforth
authors.forename: Joanne R
authors.initials: JR
authors.lastname: Flavell
authors.forename: Martin
authors.initials: M
authors.lastname: Rowe
authors.forename: A Malcolm R
authors.initials: AM
authors.lastname: Taylor
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Young
authors.forename: Paul G
authors.initials: PG
authors.lastname: Murray
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D006689:Hodgkin Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C069077:BMI1 protein, human; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D016328:NF-kappa B; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; D014763:Viral Matrix Proteins; D063150:Polycomb Repressive Complex 1; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases