Human T-cell lymphotropic virus type I (HTLV-I) transcriptional activator, Tax, enhances CREB binding to HTLV-I 21-base-pair repeats by protein-protein interaction.
Human T-cell lymphotropic virus type I (HTLV-I) transcriptional activator, Tax, enhances CREB binding to HTLV-I 21-base-pair repeats by protein-protein interaction.
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DOI：
10.1073/pnas.89.15.7070
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发表时间：
1992-08
影响因子：
11.1
通讯作者：
Ling-Jun Zhao;C. Giam
中科院分区：
文献类型：
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作者：
Ling-Jun Zhao;C. Giam
HTLV-I Tax蛋白激活病毒增强子中三个21碱基对（bp）重复序列的转录。HTLV-I 21-bp重复序列包含一个TGACGT基序，该基序与camp响应元件（CRE）同源，对税收活化至关重要。Tax对DNA表现出边际亲和力，但与细胞cre结合蛋白相互作用以增强其对HTLV-I 21-bp重复序列的亲和力。利用HTLV-I 21-bp重复序列和Jurkat t淋巴细胞核提取物进行凝胶电泳迁移试验，我们之前检测到3个蛋白- dna复合物，它们是21-bp重复序列中CRE特异性的（复合物I、II和IV）。配合物I和II与Tax相互作用，但不与IV相互作用。我们现在表明，复合物I、II和IV分别由CREB （CRE结合蛋白）同二聚体、CREB/ATF-1（激活转录因子1）异二聚体和ATF-1同二聚体组成。税收通过与CREB部分的直接相互作用来稳定复合体I和II。在没有DNA的情况下，CREB和Tax继续形成一种复合物，这种复合物可以被一种Tax特异性抗体免疫沉淀。这些结果表明，Tax激活转录的一种机制可能是通过与CREB同型二聚体和/或CREB/ATF-1异源二聚体的直接相互作用来介导的，以稳定它们在HTLV-I增强子中响应Tax的CRE基序上的组装。
HTLV-I Tax protein activates transcription from three 21-base-pair (bp) repeat sequences in the viral enhancer. The HTLV-I 21-bp repeat contains a TGACGT motif that is homologous to the cAMP-responsive element (CRE) and crucial for tax transactivation. Tax exhibits marginal affinity for DNA but rather interacts with cellular CRE-binding proteins to enhance their affinity for the HTLV-I 21-bp repeats. Using the HTLV-I 21-bp repeat and Jurkat T-lymphocyte nuclear extract in a gel electrophoretic mobility-shift assay, we previously detected three protein-DNA complexes that are specific for the CRE in the 21-bp repeat (complexes I, II, and IV). Complexes I and II but not IV interacted with Tax. We now show that complexes I, II, and IV are composed of CREB (CRE binding protein) homodimer, CREB/ATF-1 (activating transcription factor 1) heterodimer, and ATF-1 homodimer, respectively. Tax stabilizes complexes I and II via a direct interaction with the CREB moiety. In the absence of DNA, CREB and Tax continue to form a complex that can be immunoprecipitated by a Tax-specific antibody. These results suggest that one mechanism by which Tax activates transcription may be mediated through the direct interaction with CREB homodimer and/or CREB/ATF-1 heterodimer to stabilize their assembly on the Tax-responsive CRE motifs in the HTLV-I enhancer.