Wycuff Diane R, Marriott Susan J
Dept. Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Front Biosci. 2005 Jan 1;10:620-42. doi: 10.2741/1558.
HTLV-I is a complex retrovirus that encodes a transcriptional activator, Tax, which regulates expression of the viral promoter. Tax has been shown to be both necessary and sufficient to effect immortalization and transformation of cells in culture and tumorigenesis in animal models. Tax exerts its influence through protein-protein interactions with a variety of molecular targets, including transcription factors and cofactors, histone modifying enzymes and post-translational modifying enzymes. Through these interactions, Tax disrupts cellular regulatory cascades and checkpoints designed to control a variety of systems. The result is untimely activation or repression of gene expression, inappropriate protein modifications, incorrect cell cycling, loss of adequate DNA repair capacity, and potential release of the cell from tumor suppression. Whereas for the virus these functions of Tax provide a means for successful completion of its life cycle, for the cell, they result at best in anarchy, and at worst in death of both the cell and the organism of which that cell is a part.
人类嗜T细胞病毒I型(HTLV-I)是一种复杂的逆转录病毒,它编码一种转录激活因子Tax,该因子可调节病毒启动子的表达。已证明Tax对于在培养中实现细胞永生化和转化以及在动物模型中引发肿瘤发生而言既是必要的也是充分的。Tax通过与多种分子靶点进行蛋白质-蛋白质相互作用来发挥其影响,这些靶点包括转录因子和辅助因子、组蛋白修饰酶和翻译后修饰酶。通过这些相互作用,Tax破坏了旨在控制多种系统的细胞调节级联反应和检查点。其结果是基因表达的过早激活或抑制、不适当的蛋白质修饰、不正确的细胞周期循环、DNA修复能力的丧失以及细胞从肿瘤抑制中潜在的释放。虽然对于病毒来说,Tax的这些功能为其生命周期的成功完成提供了一种手段,但对于细胞而言,它们充其量导致混乱,最糟糕的情况是导致细胞以及该细胞所属生物体的死亡。