| 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: 2011-12-21 |
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 AI064518-04/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:
|
Cell Host Microbe. 2010 Dec 16;8(6):464-6
[PMID:
21147460
]
Future Microbiol. 2011 Apr;6(4):379-83 [PMID: 21526939 ] |
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...