Multiple signal transducers and activators of transcription are induced by EBV LMP-1.
Multiple signal transducers and activators of transcription are induced by EBV LMP-1.
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DOI：
10.1016/j.virol.2004.03.007
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发表时间：
2004-05
期刊：
影响因子：
3.7
通讯作者：
Luwen Zhang;K. Hong;J. Zhang;J. Pagano
中科院分区：
文献类型：
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作者：
Luwen Zhang;K. Hong;J. Zhang;J. Pagano
EB病毒（EBV）潜伏膜蛋白1（LMP-1）是原代B细胞体外永生化所必需的。信号转导和转录激活因子（STAT）在某些癌症的发生和维持中起着关键作用。STAT蛋白，特别是STAT-1、STAT-3和STAT-5，在许多癌症中持续地酪氨酸磷酸化或激活。我们发现，EB病毒感染的III型潜伏期细胞表达EB病毒癌蛋白LMP-1，表达高水平的四种STAT（STAT-1，-2，-3和-5A），LMP-1负责诱导三种STAT（STAT-1，-2和-3）。此外，LMP-1的C末端激活区1（CTAR-1）和CTAR-2协同诱导STAT-1的表达。当CTAR-1和CTAR-2以顺式而非反式存在时，协同作用是明显的。此外，NF-κB是参与STAT-1诱导的重要因子。大多数诱导的STAT在许多细胞因子激活的关键酪氨酸残基上没有磷酸化。然而，诱导的STAT，至少是STAT-1，是有功能的，因为它可以被干扰素（IFN）激活，并可以上调IFN诱导基因。最后，STAT-1的表达而不是STAT-2和STAT-3的表达与EBV转化相关。STAT-1、STAT-2、STAT-3和STAT-5A的表达与EBV III型潜伏期的关联以及STAT-1在EBV转化过程中的表达可能是调节病毒潜伏期和细胞转化的病毒编程的一部分。
Epstein-Barr virus (EBV) latent membrane protein 1 (LMP-1) is required for EBV immortalization of primary B cells in vitro. Signal transducers and activators of transcription (STATs) play a pivotal role in the initiation and maintenance of certain cancers. STAT proteins, especially STAT-1, -3, and -5, are persistently tyrosine phosphorylated or activated in many cancers. We show here that EBV-infected type III latency cells, in which the EBV oncoprotein, LMP-1 is expressed, express high levels of four STATs (STAT-1, -2, -3, and -5A) and that LMP-1 is responsible for the induction of three (STAT-1, -2, and -3). In addition, the C-terminal activator region 1 (CTAR-1) and CTAR-2 of LMP-1 cooperatively induced the expression of STAT-1. The cooperativity was evident when CTAR-1 and CTAR-2 were present in cis, but not in trans. Furthermore, NF-κB is an essential factor involved in the induction of STAT-1. Most of the induced STATs were not phosphorylated at the critical tyrosine residue activated by many cytokines. However, the induced STATs, at least STAT-1, were functional because it could be activated by interferon (IFN) and could upregulate an IFN-inducible gene. Finally, expression of STAT-1, but not STAT-2 and -3, is associated with EBV transformation. The association of the expression of STAT-1, -2, -3, and -5A with EBV type III latency and the expression of STAT-1 in the EBV transformation process may be part of the viral programming that regulates viral latency and cellular transformation.