Alternatively spliced isoforms of TFII-I - Complex formation, nuclear translocation, and differential gene regulation
Alternatively spliced isoforms of TFII-I - Complex formation, nuclear translocation, and differential gene regulation
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DOI：
10.1074/jbc.m002980200
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发表时间：
2000-08-25
影响因子：
4.8
通讯作者：
Roy, AL
中科院分区：
文献类型：
--
作者：
Cheriyath, V;Roy, AL
TFII-I 是一种多功能磷蛋白，在转录和信号转导中发挥作用。在这里，我们报告了 TFII-I 的另外三种选择性剪接亚型的表征。利用异构体特异性抗体，我们发现与细胞质相比，异构体优先在细胞核中形成稳定的体内复合物。我们进一步证明同聚和异聚相互作用都是可能的，并且野生型和核定位缺陷突变体之间的异聚相互作用导致复合物的核转位，使我们推测复合物的形成可能有助于核转位。在功能测定中，所有四种亚型均单独与 DNA 结合，并以相似的程度反式激活报告基因。然而，尽管不同 TFII-I 亚型的共表达会导致基础活性增强，但会导致信号响应活性减弱。因此，TFII-I可能通过复合物或亚复合物的形成来差异调节其靶基因。
TFII-I is a multifunctional phosphoprotein with roles in transcription and signal transduction. Here we report characterization of three additional alternatively spliced isoforms of TFII-I. Employing isoform-specific antibodies, we show that the isoforms form a stable complex in vivo preferentially in the nucleus compared with the cytoplasm. We further show that both homomeric and heteromeric interactions are possible and that the heteromeric interactions between a wild type and a nuclear localization-deficient mutant result in nuclear translocation of the complex, leading us to postulate that complex formation might aid in nuclear translocation. In functional assays all four isoforms individually bind to DNA and transactivate reporter genes to a similar extent. However, although co-expression of different TFII-I isoforms leads to enhanced basal activity, it results in attenuated signal responsive activity. Thus, TFII-I might differentially regulate its target genes via complex or subcomplex formation.