CHARACTERIZATION OF CELLULAR FACTORS THAT INTERACT WITH THE HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I P40X-RESPONSIVE 21-BASE-PAIR SEQUENCE
CHARACTERIZATION OF CELLULAR FACTORS THAT INTERACT WITH THE HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I P40X-RESPONSIVE 21-BASE-PAIR SEQUENCE
复制标题
DOI：
10.1128/jvi.62.12.4499-4509.1988
复制
发表时间：
1988-12-01
影响因子：
5.4
通讯作者：
KHOURY, G
中科院分区：
文献类型：
--
作者：
JEANG, KT;BOROS, I;KHOURY, G
人类t细胞白血病病毒I型（HTLV-I）长末端重复序列（LTR）被病毒蛋白p40x转录激活需要一个21碱基对（bp）的序列，该序列在LTR内重复三次，该序列包含一个核心八核苷酸（TGACGTCT），该序列被认为是一个环amp （cAMP）响应元件。我们在这里证明了HTLV-I LTR可以被cAMP调节因子特异性刺激，并在HeLa细胞中鉴定了四种结合HTLV-I 21-bp序列的蛋白质。我们将其中一种细胞因子（Mr, 180,000）的体外结合和转录活性与p40x对HTLV-I LTR的反式激活联系起来。HTLV-I 21 bp序列的cAMP辛核苷酸内产生点突变，同时消除了对p40x反式激活和cAMP刺激的生物反应性。我们发现这些突变还消除了180千道尔顿的HeLa因子与HTLV-I 21-bp元件的结合。由于p40x缺乏可证实的dna结合特性，我们假设细胞蛋白可能通过信号转导途径参与了其应答启动子的反式激活。
Transcriptional activation of the human T-cell leukemia virus type I (HTLV-I) long terminal repeat (LTR) by viral protein p40x requires a 21-base-pair (bp) sequence which is repeated three times within the LTR. This sequence contains a core octanucleotide (TGACGTCT) which has been attributed to be a cyclic-AMP (cAMP)-responsive element. We demonstrate here that the HTLV-I LTR can be specifically stimulated by cAMP regulators and have identified four proteins in HeLa cells that bind to the HTLV-I 21-bp sequence. We correlated the in vitro binding and transcriptional activity of one of these cellular factors (Mr, 180,000) to the trans-activation of the HTLV-I LTR by p40x. Point mutations were generated within the cAMP octanucleotide of the HTLV-I 21-bp sequence that simultaneously abolished biological responsiveness to trans-activation by p40x and to stimulation by cAMP. We found that these mutations also eliminated the binding of the 180-kilodalton HeLa factor to the HTLV-I 21-bp element. In the absence of a demonstrable DNA-binding property for p40x, we hypothesize that cellular proteins are involved, possibly through signal transduction pathways, in its trans-activation of responsive promoters.