p16INK4A-independence of Epstein–Barr virus-induced cell proliferation and virus latency
Open Access
- 1 June 2004
- journal article
- Published by Microbiology Society in Journal of General Virology
- Vol. 85 (6) , 1381-1386
- https://doi.org/10.1099/vir.0.79831-0
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 p16INK4A 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 p16INK4A was examined. From detailed analyses of the resultant lymphoblastoid cell lines it is concluded that p16INK4A 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.Keywords
This publication has 27 references indexed in Scilit:
- The retinoblastoma tumour suppressor in development and cancerNature Reviews Cancer, 2002
- INK4a-deficient human diploid fibroblasts are resistant to RAS-induced senescenceThe EMBO Journal, 2002
- Herpesvirus Lytic Replication and the Cell Cycle: Arresting New DevelopmentsJournal of Virology, 2001
- p27KIP1 is down-regulated by two different mechanisms in human lymphoid cells undergoing apoptosisOncogene, 2000
- Tumor suppressors and oncogenes in cellular senescence☆Experimental Gerontology, 2000
- Signal Transduction Pathways Leading to Cell Cycle Arrest and Apoptosis Induced by DNA Topoisomerase PoisonsCell Biochemistry and Biophysics, 2000
- Cell cycle arrest following exposure of EBV‐immortalised B‐cells to gamma irradiation correlates with inhibition of cdk2 activityFEBS Letters, 1998
- The INK4a/ARF tumor suppressor: one gene—two products—two pathwaysTrends in Biochemical Sciences, 1998
- Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblastsProceedings of the National Academy of Sciences, 1996
- DNA sequence and expression of the B95-8 Epstein—Barr virus genomeNature, 1984