The Epstein-Barr virus encoded latent membrane protein 2A augments signaling from latent membrane protein 1
The Epstein-Barr virus encoded latent membrane protein 2A augments signaling from latent membrane protein 1
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DOI：
10.1006/viro.2001.1142
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发表时间：
2001-10-25
期刊：
影响因子：
3.7
通讯作者：
Young, LS
中科院分区：
文献类型：
--
作者：
Dawson, CW;George, JH;Young, LS
EBV 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，表明这两种蛋白可能在转化过程中合作。虽然LMP2A无法直接激活NF-B-kappa和AP-1途径，但我们发现LMP2A与LMP1的共表达导致LMP1介导的这些途径的激活显着增强。发现这种增强主要依赖于 ITAM 基序 (Y74/Y85) 中存在的酪氨酸残基，并且在较小程度上依赖于位置 112 (Y112) 的酪氨酸。随后的分析表明，LMP2A能够通过延长其半衰期来稳定和调节LMP1的周转，这种能力不需要两种蛋白质之间的直接物理相互作用，而是LMP2A对LMP1蛋白周转的间接影响的结果。这项研究强调了 LMP2A 作为上皮细胞中 LMP1 活性调节剂的重要作用。 (C) 2001 年学术出版社。
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-B-kappa 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. (C) 2001 Academic Press.