ALY, a context-dependent coactivator of LEF-1 and AML-1, is required for TCR alpha enhancer function
ALY, a context-dependent coactivator of LEF-1 and AML-1, is required for TCR alpha enhancer function
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DOI：
10.1101/gad.11.5.640
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发表时间：
1997-03-01
影响因子：
10.5
通讯作者：
Grosschedl, R
中科院分区：
文献类型：
--
作者：
Bruhn, L;Munnerlyn, A;Grosschedl, R
LEF-1是一种转录因子，通过促进多种蛋白质组装成更高级的核蛋白复合物来参与T细胞受体α（TCR α）增强子的调节。LEE-I的功能部分依赖于HMG结构域和激活结构域，HMG结构域诱导DNA螺旋的急剧弯曲，激活结构域仅在与其他增强子结合蛋白的特异性竞争中刺激转录。为了深入了解上下文依赖性激活结构域的功能，我们克隆了ALY，一种新的LEF-1相互作用蛋白。ALY是一种广泛表达的核蛋白，与LEF-1和AML-1（CBF α 2，PEBP 2 α B）的活化结构域特异性结合，后者是TCR α增强子复合物的另一种蛋白质组分。此外，ALY可以增加DNA。与LEF-1和AML蛋白结合。ALY的过表达刺激在转染的非淋巴HeLa细胞中重建的TCR α增强子复合物的活性，而反义寡核苷酸下调ALY几乎消除了T细胞中的TCR α增强子活性。与LEF-1类似，ALY可以在TCR α增强子的竞争中刺激转录，但显然当通过异源DNA结合结构域与DNA连接时不能。我们认为ALY通过促进TCR α增强子复合物中多种蛋白的功能协作来介导上下文依赖性转录激活。
LEF-1 is a transcription factor that participates in the regulation of the T-cell receptor alpha (TCR alpha) enhancer by facilitating the assembly of multiple proteins into a higher order nucleoprotein complex. The function of LEE-I is dependent, in part, on the HMG domain that induces a sharp bend in the DNA helix, and on an activation domain that stimulates transcription only in a specific contest of other enhancer-binding proteins. With the aim of gaining insight into the function of context-dependent activation domains, we cloned ALY, a novel LEF-1-interacting protein. ALY is a ubiquitously expressed, nuclear protein that specifically associates with the activation domains of LEF-1 and AML-1 (CBF alpha 2, PEBP2 alpha B), which is another protein component of the TCR alpha enhancer complex. In addition, ALY can increase DNA. binding by both LEF-1 and AML proteins. Overexpression of ALY stimulates the activity of the TCR alpha enhancer complex reconstituted in transfected nonlymphoid HeLa cells, whereas down-regulation of ALY by anti-sense oligonucleotides virtually eliminates TCR alpha enhancer activity in T cells. Similar to LEF-1, ALY can stimulate transcription in the contest of the TCR alpha enhancer but apparently not when tethered to DNA through an heterologous DNA-binding domain. We propose that ALY mediates context-dependent transcriptional activation by facilitating the functional collaboration of multiple proteins in the TCR alpha enhancer complex.