Tax ubiquitylation and sumoylation control critical cytoplasmic and nuclear steps of NF-κB activation
Tax ubiquitylation and sumoylation control critical cytoplasmic and nuclear steps of NF-κB activation
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DOI：
10.1182/blood-2005-09-3572
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发表时间：
2006-05-15
期刊：
影响因子：
20.3
通讯作者：
Bazarbachi, Ali
中科院分区：
文献类型：
--
作者：
Nasr, Rihab;Chiari, Estelle;Bazarbachi, Ali
Tax癌蛋白在人类T细胞白血病病毒I型(HTLV-I)感染的T淋巴细胞的增殖和转化中发挥重要作用，其机制包括激活核因子-kappaB途径。我们发现，胞质中Tax C末端赖氨酸的泛素化对于Tax与IkappaB激酶复合体的结合以及随后的RelA的核转位至关重要。相反，我们证明了相同的赖氨酸在细胞核中被求和化，这是形成REIA-p300丰富的Tax核体和完全转录激活NF-kappa B所必需的事件。相反，Tax泛素化和总甲基化对于其激活依赖于CREB的基因来说是不必要的。因此，相同的Tax残基的泛素化和SUMO化调控着控制NF-kappa B激活的两个基本步骤，展示了这些翻译后修饰如何协同促进税收诱导的转化。
The Tax oncoprotein plays a crucial role in the proliferation and transformation of human T-cell leukemia virus type I (HTLV-I)-infected T lymphocytes through various mechanisms, including activation of the nuclear factor (NF)-kappa B pathway. We found that cytoplasmic ubiquitylation of Tax C-terminal lysines is critical for Tax binding to the IkappaB kinase complex and subsequent nuclear translocation of RelA. Conversely, we demonstrate that the same lysines are sumoylated in the nucleus, an event required for the formation of ReIA-p300-enriched Tax nuclear bodies and full NF-kappa B transcriptional activation. In contrast, Tax ubiquitylation and sumoylation are dispensable for its activation of cyclic adenosine monophosphate response element binding protein (CREB)-dependent genes. Thus, ubiquitylation and sumoylation of the same residues of Tax regulate 2 essential steps controlling NF-kappa B activation, demonstrating how these post-translational modifications can cooperate to promote Tax-induced transformation.