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PMID: 15827164 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S.

Modulation of the cell growth regulator mTOR by Epstein-Barr virus-encoded LMP2A.

Journal of virology ·Vol. 79 ·No. 9 ·2005-05-00 ·Pages 5499-506

Moody CA, Scott RS, Amirghahari N, Nathan CO, Young LS, Dawson CW, Sixbey JW

Abstract

Control of translation initiation is one means by which cells regulate growth and proliferation, with components of the protein-synthesizing machinery having oncogenic potential. Expression of latency protein LMP2A by the human tumor virus Epstein-Barr virus (EBV) activates phosphatidylinositol 3-kinase/Akt located upstream of an essential mediator of growth signals, mTOR (mammalian target of rapamycin). We show that mTOR is activated by expression of LMP2A in carcinoma cells, leading to wortmannin- and rapamycin-sensitive inhibition of the negative regulator of translation, eukaryotic initiation factor 4E-binding protein 1, and increased c-Myc protein translation. Intervention by this DNA tumor virus in cellular translational controls is likely to be an integral component of EBV tumorigenesis.

MeSH Terms
Adaptor Proteins, Signal Transducing Androstadienes/pharmacology Carrier Proteins/metabolism Cell Cycle Proteins Cell Line, Tumor Cell Proliferation Enzyme Activation/drug effects Enzyme Inhibitors/pharmacology Eukaryotic Initiation Factor-1/biosynthesis Herpesvirus 4, Human/genetics,physiology Humans Phosphatidylinositol 3-Kinases/metabolism Phosphoinositide-3 Kinase Inhibitors Phosphoproteins/metabolism Protein Kinases/metabolism Proto-Oncogene Proteins c-myc/biosynthesis Signal Transduction Sirolimus/pharmacology TOR Serine-Threonine Kinases Viral Matrix Proteins/biosynthesis,genetics,physiology Wortmannin
Chemicals
Adaptor Proteins, Signal Transducing Androstadienes Carrier Proteins Cell Cycle Proteins EBV-associated membrane antigen, Epstein-Barr virus EIF4EBP1 protein, human Enzyme Inhibitors Eukaryotic Initiation Factor-1 MYC protein, human Phosphoinositide-3 Kinase Inhibitors Phosphoproteins Proto-Oncogene Proteins c-myc Viral Matrix Proteins Protein Kinases MTOR protein, human TOR Serine-Threonine Kinases Sirolimus Wortmannin
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Moody Cary A
Microbiology and Immunology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA.
Scott Rona S
Amirghahari Nazanin
Nathan Cherie-Ann
Young Lawrence S
Dawson Chris W
Sixbey John W
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.79.9.5499-5506.2005
Published
2005-05-00
Pages
5499-506
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC1082717
Subset
IM
Grants
NCRR NIH HHS · P20 RR018724 · United States
NCI NIH HHS · R01 CA067372 · United States
NCI NIH HHS · CA67372 · United States
NCRR NIH HHS · P20RR18724 · United States
External Links
PubMed source DOI: 10.1128/JVI.79.9.5499-5506.2005 PMC Full Text View journal details
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