Activation of the lytic program of the Epstein-Barr virus in Burkitt's lymphoma cells leads to a two steps downregulation of expression of the proapoptotic protein BimEL, one of which is EBV-late-gene expression dependent.
The Epstein-Barr virus (EBV) generally latently infects its target cells with expression of genes conferring resistance to apoptosis. However, the modulation of apoptotic signals during lytic cycle remains poorly understood. We show here that resulting from viral reactivation in the EBV-positive Mutu-I and Akata Burkitt's lymphoma cell lines, a two steps proteasome-dependent downregulation of expression of the proapoptotic protein BimEL occurs. The first drop might be EBV-independent, is ERK 1/2 dependent, and BimEL is phosphorylated on Ser69. A second dramatic drop of the BimEL level observed during the lytic cycle is dependent of EBV-late-gene expression, ERK 1/2 independent, and no further phosphorylation of BimEL on Ser69 occurred. These results demonstrate for the first time, that the lytic cycle contributes to downregulation of BimEL and then could add to protection against apoptosis.
Oussaief
Lassad
L
UMR 542 Inserm-Université Paris 11, Hôpital Paul Brousse, 14 avenue Paul Vaillant Couturier, 94800 Villejuif Cedex, France.
Hippocrate
Aurélie
A
Clybouw
Cyril
C
Rampanou
Aurore
A
Ramirez
Vanessa
V
Desgranges
Claude
C
Vazquez
Aimé
A
Khelifa
Ridha
R
Joab
Irène
I
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D000072224:Bcl-2-Like Protein 11; D001897:Boronic Acids / Q000494:pharmacology; D002051:Burkitt Lymphoma; D002070:Butadienes / Q000494:pharmacology; D045744:Cell Line, Tumor; D015536:Down-Regulation; D004791:Enzyme Inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D014775:Virus Activation
D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; D001897:Boronic Acids; D002070:Butadienes; D004791:Enzyme Inhibitors; C423917:MG 262; D008565:Membrane Proteins; D009570:Nitriles; D011518:Proto-Oncogene Proteins; C113580:U 0126; D048049:Extracellular Signal-Regulated MAP Kinases