Department of Internal Medicine, American University of Beirut, Beirut, Lebanon.
Blood. 2011 Jan 6;117(1):190-9. doi: 10.1182/blood-2010-05-285742. Epub 2010 Oct 19.
The human T-lymphotropic virus type I oncoprotein Tax is critical for T-cell transformation, acting mainly through nuclear factor kappa B essential modulator (NEMO) binding and subsequent nuclear factor-κB activation. Tax localizes to Tax nuclear bodies and to the centrosome and is subjected to ubiquitylation and small ubiquitin-like modifier (SUMO)ylation, which are both necessary for complete transcriptional activation. Using the photoconvertible fluorophore Dendra-2 coupled with live video confocal microscopy, we show for the first time that the same Tax molecule shuttles among Tax nuclear bodies and between these nuclear bodies and the centrosome, depending on its posttranslational modifications. Ubiquitylation targets Tax to nuclear bodies to which NEMO is recruited and subsequently SUMOylated. We also demonstrate that Tax nuclear bodies contain the SUMOylation machinery including SUMO and the SUMO conjugating enzyme Ubc9, strongly suggesting that these nuclear bodies represent sites of active SUMOylation. Finally, both ubiquitylation and SUMOylation of Tax control NEMO targeting to the centrosome. Altogether, we are proposing a model where both ubiquitylation and SUMOylation of Tax control the shuttling of Tax and NEMO between the cytoplasmic and nuclear compartments.
人类 T 淋巴细胞白血病病毒 I 型癌蛋白 Tax 对于 T 细胞转化至关重要，主要通过核因子 κB 必需调节剂（NEMO）结合和随后的核因子-κB 激活起作用。Tax 定位于 Tax 核体和中心体，并经历泛素化和小泛素样修饰（SUMO）化，这两者对于完全转录激活都是必需的。使用光转化荧光蛋白 Dendra-2 结合活视频共聚焦显微镜，我们首次表明，相同的 Tax 分子根据其翻译后修饰在 Tax 核体之间以及这些核体与中心体之间穿梭。泛素化将 Tax 靶向到 NEMO 被募集的核体，随后 SUMO 化。我们还证明 Tax 核体包含 SUMO 化机制，包括 SUMO 和 SUMO 连接酶 Ubc9，强烈表明这些核体代表活跃 SUMO 化的部位。最后，Tax 的泛素化和 SUMO 化都控制了 NEMO 靶向中心体。总的来说，我们提出了一个模型，其中 Tax 的泛素化和 SUMO 化都控制了 Tax 和 NEMO 在细胞质和核区室之间的穿梭。
