Sequence requirements of ATF2 and CREB binding to the human T-cell leukemia virus type 1 LTR R region.

Sequence requirements of ATF2 and CREB binding to the human T-cell leukemia virus type 1 LTR R region.
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ATF2 和 CREB ​​与人类 T 细胞白血病病毒 1 型 LTR R 区结合的序列要求。

DOI:
10.1006/viro.1996.0205
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发表时间:
1996
期刊:
Virology.
影响因子:
--
通讯作者:
Nerenberg,MI
Nerenberg,MI
中科院分区:
--
文献类型:
--
作者:
Xu,X;Kang,SH;Heidenreich,O;Brown,DA;Nerenberg,MI

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我们已经确定了HTLV-1 LTR R区域的远端部分内的关键转录因子接触位点。该区域内的单碱基取代大大减少了我们先前描述为与CREB样蛋白相互作用的70-kDa核蛋白的复合物的形成。从分散的地理位置获得的HTLV-1分离株的已发表序列的比较显示,在U 5交界处附近的8个碱基片段中的簇状突变实际上是自然发生的。将对应于常见天然存在的突变的单碱基取代引入HTLV-1-LTR Cat构建体的R区。当与野生型LTR启动子相比时,这导致在表达高水平的R区结合复合物的细胞系中启动子的去阻遏。亲和纯化和电泳迁移率超位移分析确定了一个占主导地位的70 kDa的DNA结合蛋白ATF-2。磷酸化ATF-2显然与CREB相互作用形成这种下游复合物。
We have identified crucial transcription factor contact sites within the distal portion of the HTLV-I LTR R region. Single base substitutions within this region greatly reduce formation of a complex which we previously described as a 70-kDa nuclear protein interacting with a CREB-like protein. Comparison of published sequences of HTLV-1 isolates obtained from scattered geographic locations revealed that clustered mutations in an 8-base segment near the U5 junction do, in fact, occur naturally. A single base substitution corresponding to a common naturally occurring mutation was introduced into the R region of an HTLV-1-LTR Cat construct. This resulted in derepression of the promoter in a cell line expressing high levels of the R region binding complex when compared to the wild-type LTR promoter. Affinity purification and electrophoretic mobility super-shift analysis identified a dominant 70-kDa DNA binding protein as ATF-2. Phosphorylated ATF-2 apparently interacts with CREB to form this downstream complex.