Modulation of the cell growth regulator mTOR by Epstein-Barr virus-encoded LMP2A.
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.
Moody
Cary A
CA
Microbiology and Immunology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA.
Scott
Rona S
RS
Amirghahari
Nazanin
N
Nathan
Cherie-Ann
CO
Young
Lawrence S
LS
Dawson
Chris W
CW
Sixbey
John W
JW
D048868:Adaptor Proteins, Signal Transducing; D000730:Androstadienes / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015977:Eukaryotic Initiation Factor-1 / Q000096:biosynthesis; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010750:Phosphoproteins / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases; D014763:Viral Matrix Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000077191:Wortmannin
D048868:Adaptor Proteins, Signal Transducing; D000730:Androstadienes; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D015977:Eukaryotic Initiation Factor-1; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010750:Phosphoproteins; D011494:Protein Kinases; D016271:Proto-Oncogene Proteins c-myc; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; D014763:Viral Matrix Proteins; D000077191:Wortmannin; C037662:EBV-associated membrane antigen, Epstein-Barr virus; C087000:EIF4EBP1 protein, human; C489427:MYC protein, human; C546842:MTOR protein, human