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EBV Infection of Human B Lymphocytes Leads to Down-Regulation of Bim Expression: Relationship to Resistance to Apoptosis
Ist Teil von
The Journal of immunology (1950), 2005-09, Vol.175 (5), p.2968-2973
Ort / Verlag
United States: Am Assoc Immnol
Erscheinungsjahr
2005
Quelle
Free E-Journal (出版社公開部分のみ)
Beschreibungen/Notizen
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.