Expression of the Epstein Barr virus transforming protein LMP1 causes a rapid and transient stimulation of the Bcl-2 homologue Mcl-1 levels in B-cell lines.
The EBV-encoded latent membrane protein 1 (LMP1) suppresses apoptosis in B lymphocytes through up-regulation of Bcl-2. However, the maximum induction of Bcl-2 by LMP1 takes about 48-72 h. We show in this report that up-regulation of the Bcl-2 homologue Mcl-1 by LMP1 preceded the induction of Bcl-2 and that the up-regulation was transient; therefore, Mcl-1 levels decreased when Bcl-2 levels started to increase. This finding supports the hypothesis that Mcl-1 functions as a rapidly inducible, short-term effector of cell viability. LMP1 also blocked the decline in the Mcl-1 levels in response to apoptotic stimulation triggered by elevated cyclic AMP. This effect of LMP1 was associated with a delayed cell death in the EBV-negative Burkitt lymphoma cell line BL41. The maintenance of Mcl-1 expression by LMP1 is likely to be a crucial immediate-early response that enables cells to survive until Bcl-2 can be up-regulated.
Wang
S
S
Department of Cell and Molecular Biology, Umeå University, Sweden.
Rowe
M
M
Lundgren
E
E
D017209:Apoptosis / Q000502:physiology*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002104:Cadmium / Q000494:pharmacology; D002460:Cell Line; D006801:Humans; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D013997:Time Factors; D014763:Viral Matrix Proteins / Q000378:metabolism*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014763:Viral Matrix Proteins; D002104:Cadmium