Dawson C W, George J H, Blake S M, Longnecker R, Young L S
CRC Institute for Cancer Studies, University of Birmingham Medical School, Birmingham, B15 2TJ, United Kingdom.
Virology. 2001 Oct 25;289(2):192-207. doi: 10.1006/viro.2001.1142.
The frequent coexpression of the EBV-encoded latent membrane proteins LMP1 and LMP2A/B in virus-associated tumors suggests that these two proteins may cooperate in the transformation process. While LMP2A is unable to directly activate the NF-kappaB and AP-1 pathways, we found that coexpression of LMP2A with LMP1 resulted in a significant enhancement of LMP1-mediated activation of these pathways. This enhancement was found to be critically dependent on the tyrosine residues present within the ITAM motif (Y74/Y85) and, to a lesser extent, the tyrosine at position 112 (Y112). Subsequent analysis revealed that LMP2A is able to stabilize and modulate the turnover of LMP1 by extending its half-life. This ability does not require a direct physical interaction between the two proteins but rather, results from an indirect effect of LMP2A on the turnover of the LMP1 protein. This study highlights an important role for LMP2A as a modulator of LMP1 activity in epithelial cells.
EB病毒编码的潜伏膜蛋白LMP1和LMP2A/B在病毒相关肿瘤中频繁共表达，这表明这两种蛋白可能在转化过程中协同作用。虽然LMP2A无法直接激活NF-κB和AP-1信号通路，但我们发现LMP2A与LMP1共表达会导致LMP1介导的这些信号通路激活显著增强。这种增强被发现关键依赖于ITAM基序内的酪氨酸残基（Y74/Y85），在较小程度上还依赖于第112位的酪氨酸（Y112）。后续分析表明，LMP2A能够通过延长LMP1的半衰期来稳定和调节其周转。这种能力并不需要两种蛋白之间直接的物理相互作用，而是由LMP2A对LMP1蛋白周转的间接作用导致的。这项研究突出了LMP2A作为上皮细胞中LMP1活性调节剂的重要作用。
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