Sp3 encodes multiple proteins that differ in their capacity to stimulate or repress transcription
Sp3 encodes multiple proteins that differ in their capacity to stimulate or repress transcription
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DOI：
10.1093/nar/25.15.3110
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发表时间：
1997-08-01
影响因子：
14.9
通讯作者：
Horowitz, JM
中科院分区：
文献类型：
--
作者：
Kennett, SB;Udvadia, AJ;Horowitz, JM
视网膜母细胞瘤(Rb)易感基因的产物(RE-I)通过称为视网膜母细胞瘤控制元件(RCEs)的离散启动子元件来调节多种生长控制基因的表达，我们先前已经证明RCEs受一组普遍表达的115、95和80 kDa的核蛋白结合和调节，称为视网膜母细胞瘤控制蛋白(RCPs)。我们还确定了Sp转录因子家族中的两个成员Sp3和Sp1分别编码115和95 kDa的RCPs，Rb在体内刺激Sp1/SP3介导的转录。在这份报告中，我们扩展了这些结果，确定了80 kDa的RCP来自SP3 mRNA，通过位于SP3反式激活结构域内的两个内部位点进行翻译起始，内部启动的SP3蛋白在体外很容易与Sp1结合，但在体内几乎没有刺激Sp调节基因转录的能力，相反，这些SP3衍生的蛋白作为Sp1/SP3介导的转录的明显抑制物。由于细胞周期或信号诱导的多种基因的表达，包括P21(waf1/cip1)、p15(INK4B)、CYP11A、mdr1和乙酰辅酶A羧基酶，已被映射到与Sp家族成员结合的富含CC的启动子元件，我们推测内部启动的SP3亚型的蛋白质和/或DNA结合活性的改变可能是导致这些差异表达基因的调节的部分原因。
The product of the retinoblastoma (Rb) susceptibility gene (RE-I) regulates expression of a variety of growth control genes via discrete promoter elements termed retinoblastoma control elements (RCEs), We have previously shown that RCEs are bound and regulated by a common set of ubiquitously expressed nuclear proteins of 115, 95 and 80 kDa, termed retinoblastoma control proteins (RCPs), We have also previously determined that Sp3 and Sp1, two members of the Sp family of transcription factors, encode the 115 and 95 kDa RCPs respectively and that Rb stimulates Sp1/Sp3-mediated transcription in vivo. In this report we have extended these results by determining that the 80 kDa RCP arises from Sp3 mRNA via translational initiation at two internal sites located within the Sp3 trans-activation domain, internally initiated Sp3 proteins readily bind to Sp1 binding sites in vitro yet have little or no capacity to stimulate transcription of Sp-regulated genes in vivo, instead, these Sp3-derived proteins function as patent inhibitors of Sp1/Sp3-mediated transcription. Since cell cycle- or signal-induced expression of a variety of genes, including P21(waf1/cip1), p15(INK4B), CYP11A, mdr1 and acetyl-CoA carboxylase, have been mapped to CC-rich promoter elements that bind Sp family members, we speculate that alterations of the protein and/or DNA binding activities of internally initiated Sp3 isoforms may account in part: for the regulation of such differentially expressed genes.