Imperial College London

Dr Rob White

Faculty of MedicineDepartment of Medicine

Non-Clinical Lecturer in Virology
 
 
 
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Contact

 

+44 (0)20 7594 1124robert.e.white Website

 
 
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Location

 

308Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Skalska:2013:10.1371/journal.ppat.1003187,
author = {Skalska, L and White, RE and Parker, GA and Turro, E and Sinclair, AJ and Paschos, K and Allday, MJ},
doi = {10.1371/journal.ppat.1003187},
journal = {PLoS Pathog},
title = {Induction of p16(INK4a) is the major barrier to proliferation when Epstein-Barr virus (EBV) transforms primary B cells into lymphoblastoid cell lines.},
url = {http://dx.doi.org/10.1371/journal.ppat.1003187},
volume = {9},
year = {2013}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - To explore the role of p16(INK4a) as an intrinsic barrier to B cell transformation by EBV, we transformed primary B cells from an individual homozygous for a deletion in the CDKN2A locus encoding p16(INK4a) and p14(ARF). Using recombinant EBV-BAC viruses expressing conditional EBNA3C (3CHT), we developed a system that allows inactivation of EBNA3C in lymphoblastoid cell lines (LCLs) lacking active p16(INK4a) protein but expressing a functional 14(ARF)-fusion protein (p14/p16). The INK4a locus is epigenetically repressed by EBNA3C--in cooperation with EBNA3A--despite the absence of functional p16(INK4a). Although inactivation of EBNA3C in LCLs from normal B cells leads to an increase in p16(INK4a) and growth arrest, EBNA3C inactivation in the p16(INK4a)-null LCLs has no impact on the rate of proliferation, establishing that the repression of INK4a is a major function of EBNA3C in EBV-driven LCL proliferation. This conditional LCL system allowed us to use microarray analysis to identify and confirm genes regulated specifically by EBNA3C, independently of proliferation changes modulated by the p16(INK4a)-Rb-E2F axis. Infections of normal primary B cells with recombinant EBV-BAC virus from which EBNA3C is deleted or with 3CHT EBV in the absence of activating ligand 4-hydroxytamoxifen, revealed that EBNA3C is necessary to overcome an EBV-driven increase in p16(INK4a) expression and concomitant block to proliferation 2-4 weeks post-infection. If cells are p16(INK4a)-null, functional EBNA3C is dispensable for the outgrowth of LCLs.
AU - Skalska,L
AU - White,RE
AU - Parker,GA
AU - Turro,E
AU - Sinclair,AJ
AU - Paschos,K
AU - Allday,MJ
DO - 10.1371/journal.ppat.1003187
PY - 2013///
TI - Induction of p16(INK4a) is the major barrier to proliferation when Epstein-Barr virus (EBV) transforms primary B cells into lymphoblastoid cell lines.
T2 - PLoS Pathog
UR - http://dx.doi.org/10.1371/journal.ppat.1003187
UR - http://www.ncbi.nlm.nih.gov/pubmed/23436997
VL - 9
ER -