Lukac D M, Alwine J C
Department of Microbiology, Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6142, USA.
J Virol. 1999 Apr;73(4):2825-31. doi: 10.1128/JVI.73.4.2825-2831.1999.
The major immediate-early (MIE) gene of human cytomegalovirus (HCMV) encodes several MIE proteins (MIEPs) produced as a result of alternative splicing and polyadenylation of the primary transcript. Previously we demonstrated that the HCMV MIEPs expressed from the entire MIE gene could rescue the temperature-sensitive (ts) transcriptional defect in the ts13 cell line. This defect is caused by a ts mutation in TAFII250, the 250-kDa TATA binding protein-associated factor (TAF). These and other data suggested that the MIEPs perform a TAF-like function in complex with the basal transcription factor TFIID. In addition to the transcriptional defect, the ts mutation in ts13 cells results in a defect in cell cycle progression which ultimately leads to apoptosis. Since all of these defects can be rescued by wild-type TAFII250, we asked whether the MIEPs could rescue the cell cycle defect and/or affect the progression to apoptosis. We have found that the MIEPs, expressed from the entire MIE gene, do not rescue the cell cycle block in ts13 cells grown at the nonpermissive temperature. However, despite the maintenance of the cell cycle block, the ts13 cells which express the MIEPs are resistant to apoptosis. MIEP mutants, which have previously been shown to be defective in rescuing the ts transcriptional defect, maintained the ability to inhibit apoptosis. Hence, the MIEP functions which affect transcription appear to be separable from the functions which inhibit apoptosis. We discuss these data in the light of the HCMV life cycle and the possibility that the MIEPs promote cellular transformation by a "hit-and-run" mechanism.
人类巨细胞病毒（HCMV）的主要立即早期（MIE）基因编码几种MIE蛋白（MIEP），这些蛋白是初级转录本选择性剪接和多聚腺苷酸化的产物。此前我们证明，从整个MIE基因表达的HCMV MIEP可以挽救ts13细胞系中的温度敏感（ts）转录缺陷。这种缺陷是由TAFII250（一种250 kDa的TATA结合蛋白相关因子，TAF）中的ts突变引起的。这些以及其他数据表明，MIEP与基础转录因子TFIID形成复合物时发挥类似TAF的功能。除了转录缺陷外，ts13细胞中的ts突变还导致细胞周期进程缺陷，最终导致细胞凋亡。由于所有这些缺陷都可以被野生型TAFII250挽救，我们询问MIEP是否可以挽救细胞周期缺陷和/或影响细胞凋亡进程。我们发现，从整个MIE基因表达的MIEP不能挽救在非允许温度下生长的ts13细胞中的细胞周期阻滞。然而，尽管细胞周期阻滞持续存在，但表达MIEP的ts13细胞对细胞凋亡具有抗性。先前已证明在挽救ts转录缺陷方面存在缺陷 的MIEP突变体，仍保持抑制细胞凋亡的能力。因此，影响转录的MIEP功能似乎与抑制细胞凋亡的功能是可分离的。我们根据HCMV生命周期以及MIEP通过“打了就跑”机制促进细胞转化的可能性来讨论这些数据。
