The HBZ-SP1 isoform of human T-cell leukemia virus type I represses JunB activity by sequestration into nuclear bodies.
The HBZ-SP1 isoform of human T-cell leukemia virus type I represses JunB activity by sequestration into nuclear bodies.
复制标题
DOI：
10.1186/1742-4690-4-14
复制
发表时间：
2007-02-16
期刊：
影响因子：
3.3
通讯作者：
Mesnard JM
中科院分区：
文献类型：
--
作者：
Hivin P;Basbous J;Raymond F;Henaff D;Arpin-André C;Robert-Hebmann V;Barbeau B;Mesnard JM
人类T细胞白血病病毒I型（HTLV-I）碱性亮氨酸拉链因子（HBZ）先前已被证明可调节Jun家族成员的转录活性。最近在成人T细胞白血病（ATL）细胞中发现了一种新的HBZ亚型，称为HBZ-SP1，并发现其与强烈的核斑点有关。在这项研究中，我们研究了这些核小体在调节JunB转录活性中的作用。使用荧光显微镜，我们发现HBZ-SP1蛋白定位于对应于HBZ-NB和核仁的密集点。我们使用光漂白后荧光恢复（FRAP）分析来分析EGFP-HBZ-SP1融合蛋白的相对迁移率，并且发现ZIP结构域的缺失扰乱了HBZ-SP1蛋白与HBZ-NB的缔合。这些数据表明，HBZ需要细胞伴侣，包括bZIP因子，以形成HBZ-NB。事实上，通过COS细胞中的共转染实验，我们发现bZIP因子JunB能够将HBZ的离域形式（在其核定位亚结构域中缺失）靶向到HBZ-NB中。我们还表明，病毒蛋白能够引起JunB重新分布到HBZ-NB中。此外，通过用表达HBZ-SP1的载体转染HeLa细胞（已知表达高水平的JunB），JunB与HBZ-NB的隔离抑制了其转录活性。最后，我们分析了HBZ-SP1在JunD存在下的核分布，JunD是已知被HBZ激活的Jun家族成员。在这种情况下，没有检测到NB，HBZ-SP1蛋白弥漫分布在整个核质中。我们的研究结果表明，HBZ介导的隔离的JunB的HBZ-NB可能会导致抑制体内JunB的活性。
The human T-cell leukemia virus type I (HTLV-I) basic leucine-zipper factor (HBZ) has previously been shown to modulate transcriptional activity of Jun family members. The presence of a novel isoform of HBZ, termed HBZ-SP1, has recently been characterized in adult T-cell leukemia (ATL) cells and has been found to be associated with intense nuclear spots. In this study, we investigated the role of these nuclear bodies in the regulation of the transcriptional activity of JunB. Using fluorescence microscopy, we found that the HBZ-SP1 protein localizes to intense dots corresponding to HBZ-NBs and to nucleoli. We analyzed the relative mobility of the EGFP-HBZ-SP1 fusion protein using fluorescence recovery after photobleaching (FRAP) analysis and found that the deletion of the ZIP domain perturbs the association of the HBZ-SP1 protein to the HBZ-NBs. These data suggested that HBZ needs cellular partners, including bZIP factors, to form HBZ-NBs. Indeed, by cotransfection experiments in COS cells, we have found that the bZIP factor JunB is able to target delocalized form of HBZ (deleted in its nuclear localization subdomains) into the HBZ-NBs. We also show that the viral protein is able to entail a redistribution of JunB into the HBZ-NBs. Moreover, by transfecting HeLa cells (known to express high level of JunB) with a vector expressing HBZ-SP1, the sequestration of JunB to the HBZ-NBs inhibited its transcriptional activity. Lastly, we analyzed the nuclear distribution of HBZ-SP1 in the presence of JunD, a Jun family member known to be activated by HBZ. In this case, no NBs were detected and the HBZ-SP1 protein was diffusely distributed throughout the nucleoplasm. Our results suggest that HBZ-mediated sequestration of JunB to the HBZ-NBs may be causing the repression of JunB activity in vivo.
登录
查看更多内容
影响因子：
4.8
作者：
Basbous, J;Arpin, C;Mesnard, JM
通讯作者：
Mesnard, JM
影响因子：
20.3
作者：
Mesnard, Jean-Michel;Barbeau, Benoit;Devaux, Christian
通讯作者：
Devaux, Christian
影响因子：
4.8
作者：
Fatyol, K;Szalay, AA
通讯作者：
Szalay, AA
影响因子：
3.3
作者：
Hivin P;Basbous J;Raymond F;Henaff D;Arpin-André C;Robert-Hebmann V;Barbeau B;Mesnard JM
通讯作者：
Mesnard JM
影响因子：
3.3
作者：
Gallo RC
通讯作者：
Gallo RC