Wang S, Rowe M, Lundgren E
Department of Cell and Molecular Biology, Umeå University, Sweden.
Cancer Res. 1996 Oct 15;56(20):4610-3.
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.
EB病毒编码的潜伏膜蛋白1（LMP1）通过上调Bcl-2来抑制B淋巴细胞的凋亡。然而，LMP1对Bcl-2的最大诱导作用需要约48至72小时。我们在本报告中表明，LMP1对Bcl-2同源物Mcl-1的上调先于Bcl-2的诱导，且这种上调是短暂的；因此，当Bcl-2水平开始升高时，Mcl-1水平下降。这一发现支持了以下假设：Mcl-1作为细胞活力的快速诱导性短期效应因子发挥作用。LMP1还阻止了因环磷酸腺苷升高引发的凋亡刺激而导致的Mcl-1水平下降。LMP1的这一作用与EBV阴性的伯基特淋巴瘤细胞系BL41中细胞死亡延迟有关。LMP1对Mcl-1表达的维持可能是一种关键的早期即时反应，使细胞能够存活至Bcl-2上调。
