FUNCTIONAL INTERACTIONS BETWEEN YY1 AND ADENOVIRUS E1A
FUNCTIONAL INTERACTIONS BETWEEN YY1 AND ADENOVIRUS E1A
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DOI：
10.1093/nar/23.6.925
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发表时间：
1995-03-25
影响因子：
14.9
通讯作者：
SHI, Y
中科院分区：
文献类型：
--
作者：
LEE, JS;SEE, RH;SHI, Y
YY1是一种c2h2型锌指转录因子，是人GLI-Kruppel蛋白家族的成员。YY1在转录起始位点上游结合时抑制转录。这种抑制可通过腺病毒E1A解除，并激活靶基因。我们已经将YY1的抑制域映射到c端区域，重叠了它的DNA结合域。我们还在YY1的前69个氨基酸中发现了一个激活域。YY1 c端区域参与与E1A的物理相互作用，并且在功能上是YY1对E1A作出反应所必需的。这表明E1A对YY1抑制的缓解涉及到YY1-E1A的物理相互作用。虽然不参与与E1A的相互作用，但n端激活域也是YY1响应E1A所必需的。据推测，在抑制条件下，激活结构域被YY1的构象所掩盖，但在与E1A结合时被释放，并随后激活转录。与这一假设相一致，ATF-2-YY1嵌合蛋白含有ATF-P的激活域和三分之二的YY1的c端，仍然是一个有效的抑制因子。与缺乏自身n端激活域的突变体YY1不同，嵌合蛋白对E1A完全响应。
YY1 is a C2H2-type zinc finger transcription factor that is a member of the human GLI-Kruppel family of proteins. YY1 represses transcription when bound upstream of transcription initiation sites. The repression can be relieved by adenovirus E1A and activation of target genes occurs. We have mapped the repression domain of YY1 to the C-terminal region, overlapping its DNA binding domain. We have also identified an activation domain within the first 69 amino acids of YY1. The YY1 C-terminal region is involved in physical interactions with E1A and is functionally necessary for YY1 to respond to E1A. This suggests that relief of YY1 repression by E1A involves YY1-E1A physical interactions. Although not involved in interactions with E1A, the N-terminal activation domain is also necessary for YY1 to respond to E1A. Presumably, under repressing conditions, the activation domain is masked by the conformation of YY1, but is released upon binding of E1A and is required to subsequently activate transcription. Consistent with this hypothesis, an ATF-2-YY1 chimeric protein containing the activation domain of ATF-P and the C-terminal two-thirds of YY1 is still a potent repressor. Unlike the mutant YY1 lacking its own N-terminal activation domain, the chimeric protein is fully responsive to E1A.