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首页> 外文期刊>Molecular and Cellular Biology >A Conserved α-Helical Motif Mediates the Interaction of Sp1-Like Transcriptional Repressors with the Corepressor mSin3A
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A Conserved α-Helical Motif Mediates the Interaction of Sp1-Like Transcriptional Repressors with the Corepressor mSin3A

机译：一个保守的α-螺旋基元介导Sp1-like转录阻遏物与corepressor mSin3A的相互作用。

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Sp1-like proteins are defined by three highly homologous C2H2 zinc finger motifs that bind GC-rich sequences found in the promoters of a large number of genes essential for mammalian cell homeostasis. Here we report that TIEG2, a transforming growth factor β-inducible Sp1-like protein with antiproliferative functions, represses transcription through recruitment of the mSin3A-histone deacetylase complex. The interaction of TIEG2 with mSin3A is mediated by an alpha-helical repression motif (α-HRM) located within the repression domain (R1) of TIEG2. This α-HRM specifically associates with the second paired amphipathic helix (PAH2) domain of mSin3A. Mutations in the TIEG2 α-HRM domain that disrupt its helical structure abolish its ability to both bind mSin3A and repress transcription. Interestingly, the α-HRM is conserved in both the TIEG (TIEG1 and TIEG2) and BTEB (BTEB1, BTEB3, and BTEB4) subfamilies of Sp1-like proteins. The α-HRM from these proteins also mediates direct interaction with mSin3A and represses transcription. Surprisingly, we found that the α-HRM of the Sp1-like proteins characterized here exhibits structural and functional resemblance to the Sin3A-interacting domain previously described for the basic helix-loop-helix protein Mad1. Thus, our study defines a mechanism of transcriptional repression via the interactions of the α-HRM with the Sin3-histone deacetylase complex that is utilized by at least five Sp1-like transcriptional factors. More importantly, we demonstrate that a helical repression motif which mediates Sin3 interaction is not an exclusive structural and functional characteristic of the Mad1 subfamily but rather has a wider functional impact on transcriptional repression than previously demonstrated.
机译：Sp1样蛋白由三个高度同源的C 2 H 2 锌指基序定义，这些基序与在哺乳动物必需的大量基因的启动子中发现的富含GC的序列结合细胞稳态。在这里我们报告TIEG2，具有抗增殖功能的转化生长因子β诱导型Sp1样蛋白，通过招募mSin3A-组蛋白脱乙酰酶复合物来抑制转录。 TIEG2与mSin3A的相互作用是由位于TIEG2抑制域（R1）内的α-螺旋抑制基序（α-HRM）介导的。该α-HRM与mSin3A的第二对配对的两亲性螺旋（PAH2）结构域特异性结合。 TIEG2α-HRM结构域中的突变破坏了其螺旋结构，从而消除了其结合mSin3A和抑制转录的能力。有趣的是，α-HRM在Sp1样蛋白的TIEG（TIEG1和TIEG2）和BTEB（BTEB1，BTEB3和BTEB4）亚家族中都保守。这些蛋白质的α-HRM也介导与mSin3A的直接相互作用，并抑制转录。出人意料的是，我们发现此处表征为Sp1样蛋白的α-HRM与先前描述的基本螺旋-环-螺旋蛋白Mad1的Sin3A相互作用域具有结构和功能相似性。因此，我们的研究通过至少五个Sp1样转录因子利用α-HRM与Sin3-histone脱乙酰酶复合物的相互作用来定义转录抑制机制。更重要的是，我们证明了介导Sin3相互作用的螺旋阻抑基序不是Mad1亚家族的排他性结构和功能特征，而是对转录阻抑的功能影响比以前证实的更广泛。

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