EBV infection of human B lymphocytes leads to down-regulation of Bim expression: relationship to resistance to apoptosis.
EBV infects a large proportion of the human population worldwide and is one of the major viruses with human B lymphocyte tropism. It can immortalize human B lymphocytes and controls their resistance to apoptosis. EBV infection is associated with several lymphomas, including Burkitt's lymphoma. In this report we show that EBV infection leads to the post-transcriptional down-regulation of expression of the proapoptotic protein Bim. This process involves the phosphorylation of BimEL by the constitutive EBV-activated kinase ERK1/2, followed by its degradation through the proteasome pathway. We also show that ectopic expression of BimEL in EBV-positive Burkitt's lymphoma cells can enhance the sensitivity of these cells to serum deprivation-dependent apoptosis. Thus, EBV-mediated resistance to growth factor deprivation in human B lymphocytes is dependent on BimEL expression. Our data suggest that this regulatory pathway is an important contributor to the oncogenic potential of EBV.
Clybouw
Cyril
C
Institut National de la Santé et de la Recherche Médicale, Unité 542, Université Paris-Sud, Hôpital Paul Brousse, Villejuif, France.
McHichi
Bouchra
B
Mouhamad
Shahul
S
Auffredou
Marie Thérèse
MT
Bourgeade
Marie Françoise
MF
Sharma
Surendra
S
Leca
Gerald
G
Vazquez
Aimé
A
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001402:B-Lymphocytes / Q000473:pathology / Q000821:virology*; D000072224:Bcl-2-Like Protein 11; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D005786:Gene Expression Regulation; D004854:Herpesvirus 4, Human / Q000472:pathogenicity*; D006801:Humans; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D048049:Extracellular Signal-Regulated MAP Kinases