Low nuclear body formation and tax SUMOylation do not prevent NF-kappaB promoter activation.
Low nuclear body formation and tax SUMOylation do not prevent NF-kappaB promoter activation.
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DOI：
10.1186/1742-4690-9-77
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发表时间：
2012-09-25
期刊：
影响因子：
3.3
通讯作者：
Pique C
中科院分区：
文献类型：
--
作者：
Bonnet A;Randrianarison-Huetz V;Nzounza P;Nedelec M;Chazal M;Waast L;Pene S;Bazarbachi A;Mahieux R;Bénit L;Pique C
Human T-lymphotropic virus type 1 （HTLV-1）编码的Tax蛋白是NF-κB通路的强大激活剂，这是HTLV-1诱导CD4+ T淋巴细胞永生化的关键特性。在细胞质水平上，Tax通过激活ikb激酶（IKK）复合物永久性地刺激这一通路；在核水平上，通过增强NF-κB因子RelA与其同源启动子的结合，并通过形成被认为代表转录活性结构的核小体，永久地刺激这一通路。在之前的研究中，我们报道了Tax泛素化和SUMOylation在Tax定位和NF-κB激活中起着关键作用。事实上，对与泛素或SUMO融合或不融合的赖氨酸Tax突变体的分析使我们提出了一个两步模型，其中Tax泛素化首先干预激活IKK，而Tax SUMO化随后需要在Tax核体内激活启动子。然而，最近的研究表明，泛素或SUMO可以调节细胞核或细胞质中的Tax活性，并且SUMO化的Tax可以作为泛素化的底物，这表明Tax泛素化和SUMO化可能介导冗余而不是连续的功能。在这项研究中，我们分析了一个新的Tax突变体的特性，该突变体被泛素化，但核体形成和sumo化都有缺陷。我们报道，降低Tax summoylation和核体形成不会改变Tax激活IKK、诱导RelA核易位和触发NF-κB启动子基因表达的能力。重要的是，在T细胞（包括CD4+原发T淋巴细胞）中，尽管低sumo化和核体形成，但Tax也能有效激活NF-κB启动子。此外，我们发现在htlv -1感染的T细胞中几乎没有观察到Tax核体。最后，我们提供了直接证据，证明税收激活NF-κB的程度与税收泛素化水平相关，而不是sumo化水平。这些数据表明，先前与Tax转染细胞的转录活性相关的Tax核体的形成对于NF-κB启动子的激活是必不可少的，特别是在CD4+ T细胞中。他们还提供了第一个证据，证明税收summoylation不是税收诱导的NF-κB激活的关键决定因素。
The Tax protein encoded by Human T-lymphotropic virus type 1 (HTLV-1) is a powerful activator of the NF-κB pathway, a property critical for HTLV-1-induced immortalization of CD4+ T lymphocytes. Tax permanently stimulates this pathway at a cytoplasmic level by activating the IκB kinase (IKK) complex and at a nuclear level by enhancing the binding of the NF-κB factor RelA to its cognate promoters and by forming nuclear bodies, believed to represent transcriptionally active structures. In previous studies, we reported that Tax ubiquitination and SUMOylation play a critical role in Tax localization and NF-κB activation. Indeed, analysis of lysine Tax mutants fused or not to ubiquitin or SUMO led us to propose a two-step model in which Tax ubiquitination first intervenes to activate IKK while Tax SUMOylation is subsequently required for promoter activation within Tax nuclear bodies. However, recent studies showing that ubiquitin or SUMO can modulate Tax activities in either the nucleus or the cytoplasm and that SUMOylated Tax can serve as substrate for ubiquitination suggested that Tax ubiquitination and SUMOylation may mediate redundant rather than successive functions. In this study, we analyzed the properties of a new Tax mutant that is properly ubiquitinated, but defective for both nuclear body formation and SUMOylation. We report that reducing Tax SUMOylation and nuclear body formation do not alter the ability of Tax to activate IKK, induce RelA nuclear translocation, and trigger gene expression from a NF-κB promoter. Importantly, potent NF-κB promoter activation by Tax despite low SUMOylation and nuclear body formation is also observed in T cells, including CD4+ primary T lymphocytes. Moreover, we show that Tax nuclear bodies are hardly observed in HTLV-1-infected T cells. Finally, we provide direct evidence that the degree of NF-κB activation by Tax correlates with the level of Tax ubiquitination, but not SUMOylation. These data reveal that the formation of Tax nuclear bodies, previously associated to transcriptional activities in Tax-transfected cells, is dispensable for NF-κB promoter activation, notably in CD4+ T cells. They also provide the first evidence that Tax SUMOylation is not a key determinant for Tax-induced NF-κB activation.
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影响因子：
3.3
作者：
Boxus M;Twizere JC;Legros S;Dewulf JF;Kettmann R;Willems L
通讯作者：
Willems L
影响因子：
4.8
作者：
Harhaj, Nicole S.;Sun, Shao-Cong;Harhaj, Edward W.
通讯作者：
Harhaj, Edward W.
DOI：
10.1073/pnas.77.12.7415
发表时间：
1980-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
POIESZ, BJ;RUSCETTI, FW;GALLO, RC
通讯作者：
GALLO, RC
影响因子：
5.4
作者：
Fryrear, Kimberly A.;Durkin, Sarah S.;Semmes, O. John
通讯作者：
Semmes, O. John
影响因子：
5.4
作者：
Lavorgna, Alfonso;Harhaj, Edward W.
通讯作者：
Harhaj, Edward W.