Nuclear localization of HTLV-I bZIP factor (HBZ) is mediated by three distinct motifs
Nuclear localization of HTLV-I bZIP factor (HBZ) is mediated by three distinct motifs
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DOI：
10.1242/jcs.01727
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发表时间：
2005-04-01
影响因子：
4
通讯作者：
Mesnard, JM
中科院分区：
文献类型：
--
作者：
Hivin, P;Frédéric, M;Mesnard, JM
人类T细胞白血病病毒I型（HTLV-I）的基因组编码碱性亮氨酸拉链蛋白HBZ，能够抑制JUN活性和病毒转录。在哺乳动物细胞中的瞬时表达表明，HBZ靶向细胞核，在那里它积累在核斑点。通过使用一组互补的缺失突变体，我们在这里报告的核靶向HBZ介导的三个不同的核定位信号，至少有两个是必要的HBZ易位到细胞核。此外，所得到的突变蛋白分布在整个核质和/或进入核仁，而野生型HBZ专门积累在核斑点，这表明蛋白质的完整性是必需的斑点本地化。我们还表明，HBZ的斑点不对应于卡哈尔机构，剪接因子车厢，或早幼粒细胞白血病癌蛋白体。出乎意料的是，通过使用免疫金电子显微镜，我们发现HBZ定位于异染色质。到目前为止，这种特性从未被描述为转录因子，可以解释HBZ的抑制活性。
The genome of the human T-cell leukemia virus type I (HTLV-I) codes for a basic leucine zipper protein, HBZ, capable of repressing JUN activity and viral transcription. Transient expression in mammalian cells showed that HBZ was targeted to the nucleus, where it accumulated in nuclear speckles. By using a complementary set of deletion mutants, we report here that the nuclear targeting of HBZ is mediated by three distinct nuclear localization signals and that at least two are necessary for the translocation of HBZ to the nucleus. Moreover, the resulting mutant proteins distribute throughout the nucleoplasm and/or into the nucleoli, whereas the wild-type HBZ exclusively accumulates in nuclear speckles, suggesting that the integrity of the protein is required for its speckle localization. We also demonstrate that the HBZ-containing speckles do not correspond to Cajal bodies, splicing factor compartments, or promyelocytic leukemia oncoprotein bodies. Unexpectedly, by using immunogold electron microscopy, we found HBZ localized to heterochromatin. Until now, such characteristics had never been described for a transcription factor and could explain the inhibitory activity of HBZ.