title: p16(INK4A)-independence of Epstein-Barr virus-induced cell proliferation and virus latency.
abstract: Epstein-Barr virus (EBV) has the ability to promote cell cycle progression following the initial infection of primary resting B-lymphocytes and to cause cell cycle arrest at the onset of the viral replicative cycle. Various mechanisms have been proposed for the proliferative effects, including the up-regulation of cyclin D2 by the viral EBNA-2 and EBNA-LP proteins, direct binding of EBNA3C to the retinoblastoma protein (pRb), and down-regulation of the p16(INK4A) tumour suppressor by the viral LMP1 product. To try to gain insight into the relative importance of these mechanisms, the ability of EBV to immortalize lymphocytes from an individual who is genetically deficient for p16(INK4A) was examined. From detailed analyses of the resultant lymphoblastoid cell lines it is concluded that p16(INK4A) status has little bearing on EBV's ability to manipulate the cell cycle machinery and a model to accommodate the previously proposed routes taken by EBV to bypass the restriction point is presented.
authors.affiliation: School of Life Sciences, University of Sussex, Brighton BN1 9QG, UK.
authors.forename: Michelle J
authors.initials: MJ
authors.lastname: Hayes
authors.affiliation: School of Life Sciences, University of Sussex, Brighton BN1 9QG, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Koundouris
authors.affiliation: Department of Dermatology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Nelleke
authors.initials: N
authors.lastname: Gruis
authors.affiliation: Department of Dermatology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Wilma
authors.initials: W
authors.lastname: Bergman
authors.affiliation: Cancer Research UK London Research Institute, Lincolns Inn Fields, London, UK.
authors.forename: Gordon G
authors.initials: GG
authors.lastname: Peters
authors.affiliation: School of Life Sciences, University of Sussex, Brighton BN1 9QG, UK.
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Sinclair
mesh_terms: D017209:Apoptosis; D002455:Cell Division; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000502:physiology*; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D025803:Tumor Suppressor Protein p14ARF / Q000502:physiology; D017735:Virus Latency
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D025803:Tumor Suppressor Protein p14ARF