SERUM RESPONSE FACTOR HAS FUNCTIONAL ROLES BOTH IN INDIRECT BINDING TO THE CARG BOX AND IN THE TRANSCRIPTIONAL ACTIVATION FUNCTION OF HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I TAX
SERUM RESPONSE FACTOR HAS FUNCTIONAL ROLES BOTH IN INDIRECT BINDING TO THE CARG BOX AND IN THE TRANSCRIPTIONAL ACTIVATION FUNCTION OF HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I TAX
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DOI：
10.1128/jvi.68.11.7275-7283.1994
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发表时间：
1994-11-01
影响因子：
5.4
通讯作者：
SEIKI, M
中科院分区：
文献类型：
--
作者：
FUJII, M;TSUCHIYA, H;SEIKI, M
我们之前报道了人类t细胞白血病病毒I型的Tax1直接与血清反应因子（SRF）相互作用，并且Tax1通过SRF结合位点（CArG box）激活几个细胞即时早期基因的转录。这种激活需要Tax1的转录激活功能，确定为GALTax（与酵母转录因子GAL4嵌合的Tax1）在GAL4结合位点的活性。在这项研究中，我们研究了SRF是否在Tax1的转录激活功能中发挥作用。由于抑制，Tax1的表达抑制了GALTax在GAL4位点的活性，而SRF的过表达恢复了被抑制的活性，这表明SRF是GALTax活性所必需的因子，并且由于与Tax1的竞争而被抑制。反义SRF RNA的表达特异性抑制GALTax活性低于20%。SRF C端Tax1相互作用域的缺失将SRF从GALTax的激活剂转变为抑制剂。这些结果表明SRF是Tax1转录激活的重要组成部分，也是CArG盒子结合的中介。
We previously reported that Tax1 of human T-cell leukemia virus type I interacts directly with serum response factor (SRF) and that Tax1 activates the transcription of several cellular immediate-early genes through the SRF binding site (CArG box). This activation required the transcriptional activation function of Tax1, identified as an activity of GALTax (a chimeric Tax1 with the yeast transcription factor GAL4) at the GAL4-binding site. In this study, we examined whether SRF plays a role in the transcriptional activation function of Tax1. Expression of Tax1 suppressed the GALTax activity at the GAL4 site as a result of squelching, and the suppressed activity was recovered by the overexpression of SRF, suggesting that SRF is a factor that is required for GALTax activity and that is inhibited by competition with Tax1. The expression of antisense SRF RNA specifically inhibited GALTax activity to less than 20%. Deletion of the Tax1 interaction domain of SRF at its C terminus converted SRF from an activator of GALTax to an inhibitor. These results suggest that SRF is an essential component of the transcriptional activation of Tax1 in addition to a mediator of CArG box binding.