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首页> 外文期刊>Molecular and Cellular Biology >An alternatively spliced mRNA from the AP-2 gene encodes a negative regulator of transcriptional activation by AP-2.
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An alternatively spliced mRNA from the AP-2 gene encodes a negative regulator of transcriptional activation by AP-2.

机译：来自AP-2基因的另一种剪接的mRNA编码AP-2转录激活的负调控子。

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AP-2 is a retinoic acid-inducible and developmentally regulated activator of transcription. We have cloned an alternative AP-2 transcript (AP-2B) from the human teratocarcinoma cell line PA-1, which encodes a protein differing in the C terminus from the previously isolated AP-2 protein (AP-2A). This protein contains the activation domain of AP-2 and part of the DNA binding domain but lacks the dimerization domain which is necessary for DNA binding. Analysis of overlapping genomic clones spanning the entire AP-2 gene proves that AP-2A and AP-2B transcripts are alternatively spliced from the same gene. Both transient and stable transfection experiments show that AP-2B inhibits AP-2 transactivator function, as measured by an AP-2-responsive chloramphenicol acetyltransferase reporter plasmid. Furthermore, constitutive AP-2B expression in PA-1 cells causes a retinoic acid-resistant phenotype, anchorage-independent growth in soft agar, and tumorigenicity in nude mice, in a fashion similar to transformation of these cells by oncogenes. To determine the mechanism by which AP-2B exerts its inhibitory function, we purified bacterially expressed AP-2A and AP-2B proteins. While bacterial AP-2B does not bind an AP-2 consensus site, it strongly inhibits binding of the endogenous AP-2 present in PA-1 cell nuclear extracts. However, DNA sequence-specific binding of bacterially expressed AP-2A cannot be inhibited by bacterially expressed AP-2B. Therefore, inhibition of AP-2 activity by the protein AP-2B may require an additional factor or modification supplied by nuclear extracts.
机译：AP-2是视黄酸诱导和转录调控的发育活化剂。我们已经从人畸胎瘤细胞株PA-1克隆了另一种AP-2转录本（AP-2B），其编码的C末端不同于先前分离的AP-2蛋白质（AP-2A）。该蛋白质包含AP-2的激活结构域和DNA结合结构域的一部分，但缺少DNA结合所需的二聚结构域。跨越整个AP-2基因的重叠基因组克隆的分析证明，AP-2A和AP-2B转录本是从同一基因中交替剪接而成的。瞬时和稳定转染实验均显示，AP-2B可抑制AP-2反式激活子功能，这是通过对AP-2的氯霉素乙酰转移酶报告质粒进行的。此外，PA-1细胞中的本构性AP-2B表达导致视黄酸抵抗型，软琼脂中不依赖锚定的生长以及裸鼠中的致瘤性，其表达方式类似于癌基因转化这些细胞。为了确定AP-2B发挥其抑制功能的机制，我们纯化了细菌表达的AP-2A和AP-2B蛋白。虽然细菌AP-2B不结合AP-2共有位点，但它强烈抑制PA-1细胞核提取物中存在的内源性AP-2的结合。但是，细菌表达的AP-2A不能抑制DNA序列特异性结合。因此，蛋白AP-2B对AP-2活性的抑制可能需要核提取物提供的其他因子或修饰。

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