Identification of a novel transcriptional activity of mammalian Id proteins
Identification of a novel transcriptional activity of mammalian Id proteins
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DOI：
10.1093/nar/27.7.1740
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发表时间：
1999-04-01
影响因子：
14.9
通讯作者：
Christy, BA
中科院分区：
文献类型：
--
作者：
Bounpheng, MA;Melnikova, IN;Christy, BA
Id蛋白是一个相关的哺乳动物螺旋-环-螺旋（HLH）蛋白家族，它可以与其他HLH蛋白相互作用，但缺乏一个基本区域，因此不被认为与DNA结合。相反，它们被假设为dna结合碱性HLH （bHLH）蛋白的显性负调节因子，通过与这些蛋白形成非活性异源二聚体。所有四个Id家族蛋白都具有相关的HLH二聚化结构域，并且可以与类似的bHLH蛋白相互作用，尽管具有不同的亲和力。蛋白质的N端和c端大部分不相关的功能是未知的。在这项研究中，我们发现了哺乳动物Id蛋白的一种新的转录活性。我们发现，当融合到异源GAL4 dna结合域时，所有四种哺乳动物Id蛋白都可以激活GAL4依赖性转录。HLH结构域是观察到的转激活活性所必需的，这表明与细胞HLH蛋白的相互作用是必需的。与外源性A类bHLH蛋白（e蛋白）共转染大大增强了反激活，而与B类bHLH蛋白共转染则消除了反激活。这些结果与Id蛋白在dna结合复合体中具有转录活性的观点是一致的。
The Id proteins are a family of related mammalian helix-loop-helix (HLH) proteins which can interact with other HLH proteins but lack a basic region and are thus not thought to bind to DNA. Instead, they are hypothesized to act as dominant negative regulators of DNA-binding basic HLH (bHLH) proteins, by forming inactive heterodimers with these proteins. All four Id family proteins possess related HLH dimerization domains and can interact with similar bHLH proteins, although with differing affinities. The functions of the largely unrelated N- and C-terminal regions of the proteins are unknown. In this study, we have identified a novel transcriptional activity of the mammalian Id proteins. We show that when fused to the heterologous GAL4 DNA-binding domain, all four of the mammalian Id proteins can activate GAL4-dependent transcription. The HLH domain is necessary for the transactivation activity observed, suggesting that interaction with a cellular HLH protein is required. Co-transfection with exogenous Class A bHLH proteins (E-proteins) greatly potentiates the transactivation, which is abolished upon co-transfection with Class B bHLH proteins. These results are consistent with the idea that the Id proteins have a transcriptional activity when present in a DNA-binding complex.