The HBZ factor of human T-cell leukemia virus type I dimerizes with transcription factors JunB and c-Jun and modulates their transcriptional activity
The HBZ factor of human T-cell leukemia virus type I dimerizes with transcription factors JunB and c-Jun and modulates their transcriptional activity
复制标题
DOI：
10.1074/jbc.m307275200
复制
发表时间：
2003-10-31
影响因子：
4.8
通讯作者：
Mesnard, JM
中科院分区：
文献类型：
--
作者：
Basbous, J;Arpin, C;Mesnard, JM
人类T细胞白血病病毒I型（HTLV-I）编码的Tax蛋白通过与细胞碱性亮氨酸拉链因子cAMP反应元件结合蛋白-2结合激活病毒启动子的转录。Tax还能够诱导T淋巴细胞的细胞转化，可能是通过调节细胞因子的转录活性，包括核因子-κ B、E2 F、激活蛋白-1（AP-1）和p53。最近，我们在HTLV-I感染的细胞中表征了由HTLV-I RNA基因组的互补链编码的新型病毒蛋白HBZ的存在（Gaudray，G.，Gachon，F.，Basbous，J.，Biard-Piechaczyk，M.，德沃角，和Mesnard，J. - M.等人（2002）J. Virol. 76，12813-12822）。HBZ是一种核碱性亮氨酸拉链蛋白，通过抑制cAMP-反应元件结合蛋白-2与HTLV-I启动子的结合来下调Tax依赖性病毒转录。在寻找HBZ的其他细胞靶点时，我们鉴定了Jun家族的两个成员JunB和c-Jun。免疫共沉淀和细胞共定位证实HBZ与JunB和c-Jun在体内相互作用。当将含有胶原酶启动子AP-1位点的报告基因瞬时导入CEM细胞时，HBZ抑制c-Jun的反式激活。另一方面，HBZ与Jun-B的组合比JunB单独具有更高的转录活性。与其基本结构域的结构一致，我们证明HBZ降低了c-Jun和JunB的DNA结合活性。最后，我们表明，c-Jun是不再能够激活的基础表达的HTLV-I启动子在体内的HBZ的存在下。我们的研究结果支持这一假设，即HBZ可以是一个负调控的税收效应，通过控制税收的表达在转录水平和减弱激活AP-1的税收。
The human T-cell leukemia virus type I (HTLV-I)-encoded Tax protein activates transcription from the viral promoter via association with the cellular basic leucine zipper factor cAMP-response element-binding protein-2. Tax is also able to induce cellular transformation of T lymphocytes probably by modulating transcriptional activity of cellular factors, including nuclear factor-kappaB, E2F, activator protein-1 (AP-1), and p53. Recently, we characterized in HTLV-I-infected cells the presence of a novel viral protein, HBZ, encoded by the complementary strand of the HTLV-I RNA genome (Gaudray, G., Gachon, F., Basbous, J., Biard-Piechaczyk, M., Devaux, C., and Mesnard, J.-M. (2002) J. Virol. 76, 12813-12822). HBZ is a nuclear basic leucine zipper protein that downregulates Tax-dependent viral transcription by inhibiting the binding of cAMP-response element-binding protein-2 to the HTLV-I promoter. In searching for other cellular targets of HBZ, we identified two members of the Jun family, JunB and c-Jun. Co-immunoprecipitation and cellular colocalization confirmed that HBZ interacts in vivo with JunB and c-Jun. When transiently introduced into CEM cells with a reporter gene containing the AP-1 site from the collagenase promoter, HBZ suppressed transactivation by c-Jun. On the other hand, the combination of HBZ with Jun-B had higher transcriptional activity than JunB alone. Consistent with the structure of its basic domain, we demonstrate that HBZ decreases the DNA-binding activity of c-Jun and JunB. Last, we show that c-Jun is no longer capable of activating the basal expression of the HTLV-I promoter in the presence of HBZ in vivo. Our results support the hypothesis that HBZ could be a negative modulator of the Tax effect by controlling Tax expression at the transcriptional level and by attenuating activation of AP-1 by Tax.