Document Detail


An ATM/Chk2-mediated DNA damage-responsive signaling pathway suppresses Epstein-Barr virus transformation of primary human B cells.
MedLine Citation:
PMID:  21147465     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Epstein-Barr virus (EBV), an oncogenic herpesvirus that causes human malignancies, infects and immortalizes primary human B cells in vitro into indefinitely proliferating lymphoblastoid cell lines, which represent a model for EBV-induced tumorigenesis. The immortalization efficiency is very low, suggesting that an innate tumor suppressor mechanism is operative. We identify the DNA damage response (DDR) as a major component of the underlying tumor suppressor mechanism. EBV-induced DDR activation was not due to lytic viral replication, nor did the DDR marks colocalize with latent episomes. Rather, a transient period of EBV-induced hyperproliferation correlated with DDR activation. Inhibition of the DDR kinases ATM and Chk2 markedly increased transformation efficiency of primary B cells. Further, the viral latent oncoprotein EBNA3C was required to attenuate the EBV-induced DDR. We propose that heightened oncogenic activity in early cell divisions activates a growth-suppressive DDR that is attenuated by viral latency products to induce cell immortalization.
Authors:
Pavel A Nikitin; Christopher M Yan; Eleonora Forte; Alessio Bocedi; Jason P Tourigny; Robert E White; Martin J Allday; Amee Patel; Sandeep S Dave; William Kim; Katherine Hu; Jing Guo; David Tainter; Elena Rusyn; Micah A Luftig
Related Documents :
9255755 - Cell aging in vivo and in vitro.
12114965 - Telomere shortening of mcf-7 cells caused by antisense telomerase cdna.
19129235 - A role for monoubiquitinated fancd2 at telomeres in alt cells.
6530835 - Mosaic pattern changes in human corneal endothelium with age.
6187445 - Ultrastructural differentiation of a clonal human embryonal carcinoma cell line in vitro.
4063985 - Interspecies lewis lung carcinoma x chinese hamster ovary hybrids as protective agents ...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell host & microbe     Volume:  8     ISSN:  1934-6069     ISO Abbreviation:  Cell Host Microbe     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-14     Completed Date:  2011-04-06     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  101302316     Medline TA:  Cell Host Microbe     Country:  United States    
Other Details:
Languages:  eng     Pagination:  510-22     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Affiliation:
Department of Molecular Genetics and Microbiology, Center for Virology, Duke University School of Medicine, Durham, NC 27712, USA.
Data Bank Information
Bank Name/Acc. No.:
GEO/GSE20200
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
B-Lymphocytes / pathology,  virology*
Cell Cycle Proteins / physiology*
Cell Proliferation
Cell Transformation, Viral
Cells, Cultured
DNA Damage*
DNA-Binding Proteins / physiology*
Epstein-Barr Virus Nuclear Antigens / physiology
Herpesvirus 4, Human / physiology*
Humans
Protein-Serine-Threonine Kinases / physiology*
Signal Transduction
Tumor Suppressor Proteins / physiology*
Grant Support
ID/Acronym/Agency:
P30 AI064518/AI/NIAID NIH HHS; P30 AI064518-04/AI/NIAID NIH HHS; P30 AI064518-05/AI/NIAID NIH HHS; P30 AI064518-06/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins; 0/DNA-Binding Proteins; 0/Epstein-Barr Virus Nuclear Antigens; 0/Tumor Suppressor Proteins; EC 2.7.1.11/checkpoint kinase 2; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/ataxia telangiectasia mutated protein
Comments/Corrections
Comment In:
Future Microbiol. 2011 Apr;6(4):379-83   [PMID:  21526939 ]
Cell Host Microbe. 2010 Dec 16;8(6):464-6   [PMID:  21147460 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  The Ubiquitin Ligase Riplet Is Essential for RIG-I-Dependent Innate Immune Responses to RNA Virus In...
Next Document:  A Pivotal Role for CXCL12 Signaling in HPV-Mediated Transformation of Keratinocytes: Clues to Under...