Complexity of translationally controlled transcription factor Sp3 isoform expression
Complexity of translationally controlled transcription factor Sp3 isoform expression
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DOI：
10.1074/jbc.m404989200
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发表时间：
2004-10-01
影响因子：
4.8
通讯作者：
Suske, G
中科院分区：
文献类型：
--
作者：
Sapetschnig, A;Koch, F;Suske, G
Sp3是与Sp1密切相关的普遍存在的转录因子。这两种蛋白质都含有一个高度保守的DNA结合结构域接近C端和两个谷氨酰胺丰富的结构域中的N-末端部分。Sp3的免疫印迹分析揭示了多达8个不同物种的惊人的复杂蛋白质模式。在Sp3缺陷细胞系中未观察到这种模式，表明所有信号都反映Sp3抗原。在这项研究中，我们揭示了Sp3表达的复杂性。我们发现，四个亚型的Sp3保留不同部分的N端在体内表达。这四种异构体衍生自位置1、37、856和907处的替代翻译起始位点。位于-47至-18位的上游开放阅读框调节两种长同种型的表达。与Sp1不同，Sp3亚型均未被糖基化。然而，所有四种异构体在体内和体外特异性地且仅在赖氨酸残基551处变成SUMO修饰的。两种长亚型的转录活性强烈依赖于启动子设置，而小亚型似乎没有活性。所有Sp3亚型的转录活性都受到SUMO修饰的调控。我们的研究结果表明，SP3有许多独特的功能，并不是简单的功能相当于SP1。
Sp3 is a ubiquitous transcription factor closely related to Sp1. Both proteins contain a highly conserved DNA-binding domain close to the C terminus and two glutamine-rich domains in the N-terminal moiety. Immunoblot analyses of Sp3 reveal a striking complex protein pattern of up to eight distinct species. This pattern is not observed in Sp3-deficient cell lines showing that all signals reflect Sp3 antigen. In this study, we have unraveled the complexity of Sp3 expression. We show that four isoforms of Sp3 that retain different parts of the N terminus are expressed in vivo. The four isoforms derive from alternative translational start sites at positions 1, 37, 856, and 907. An upstream open reading frame located at position - 47 to - 18 regulates expression of the two long isoforms. Unlike Sp1, none of the Sp3 isoforms is glycosylated. However, all four isoforms become SUMO-modified in vivo and in vitro specifically and exclusively at lysine residue 551. The transcriptional activity of the two long isoforms strongly depends on the promoter settings, whereas the small isoforms appear to be inactive. The transcriptional activity of all the Sp3 isoforms is regulated by SUMO modification. Our results demonstrate that Sp3 has many unique features and is not simply a functional equivalent of Sp1.