Dimerization and a Novel Tax Speckled Structure Localization Signal Are Required for Tax Nuclear Localization
Dimerization and a Novel Tax Speckled Structure Localization Signal Are Required for Tax Nuclear Localization
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DOI：
10.1128/jvi.00232-09
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发表时间：
2009-06-01
影响因子：
5.4
通讯作者：
Semmes, O. John
中科院分区：
文献类型：
--
作者：
Fryrear, Kimberly A.;Durkin, Sarah S.;Semmes, O. John
人类T细胞白血病病毒1型癌蛋白Tax具有多效活性，其中一个亚类可能导致T细胞永生化。Tax在细胞核和细胞质中都有表达，并且已知其在细胞核和细胞质中发挥作用。税收已经定义了核本地化（NLS）和核出口信号，使两个隔间之间的穿梭。在这项研究中，我们确定了一个新的区域，在税收的目标蛋白质离散核灶，我们以前称为税收斑点结构（TSS）。我们证明，所确定的区域是必要的和足够的指导蛋白质的TSS。这种新的TSS定位信号（TSLS），跨越氨基酸50至75，是可分离的，并邻近NLS的税收。Tax NLS突变体和Tax TSLS突变体的共表达挽救了两种蛋白质的核进入和亚核TSS靶向，表明这些信号是独立的结构域。我们的分析还表明，税务蛋白缺乏二聚体未能本地化的细胞核。因此，当我们通过诱导异源“二聚化”结构域恢复二聚化时，核定位被拯救。因此，我们在Tax中针对核定位和亚核靶向定义了额外的域。我们的研究结果揭示了一个更复杂的网络调节税收亚细胞定位和随后的功能。
The human T-cell leukemia virus type 1 oncoprotein Tax has pleiotropic activities, a subset of which likely leads to immortalization of T cells. Tax is expressed and known to function in both the cell nucleus and the cytoplasm. Tax has defined nuclear localization (NLS) and nuclear export signals that enable shuttling between the two compartments. In this study, we identified a novel region in Tax that targets the protein to discrete nuclear foci that we have previously termed Tax speckled structures (TSS). We demonstrated that the identified region is both necessary and sufficient for directing proteins to TSS. This novel TSS localization signal (TSLS), spanning amino acids 50 to 75, is separable from and adjacent to the NLS of Tax. Coexpression of a Tax NLS mutant and a Tax TSLS mutant rescued the nuclear entry and subnuclear TSS targeting of both proteins, demonstrating that these signals are independent domains. Our analysis also revealed that Tax proteins deficient for dimerization fail to localize to the nucleus. Consequently, when we restored dimerization via induction of a heterologous "dimerizer" domain, nuclear localization was rescued. Thus, we defined additional domains in Tax specific for nuclear localization and subnuclear targeting. Our results reveal a more complex network for regulation of Tax subcellular localization and subsequent function.