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首页> 外文期刊>Molecular and Cellular Biology >Conserved Catalytic and C-Terminal Regulatory Domains of the C-Terminal Binding Protein Corepressor Fine-Tune the Transcriptional Response in Development
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Conserved Catalytic and C-Terminal Regulatory Domains of the C-Terminal Binding Protein Corepressor Fine-Tune the Transcriptional Response in Development

机译：C末端结合蛋白Corepressor的保守的催化和C末端调节域微调发展中的转录反应。

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Transcriptional corepressors play complex roles in developmental gene regulation. These proteins control transcription by recruiting diverse chromatin-modifying enzymes, but it is not known whether corepressor activities are finely regulated in different developmental settings or whether their basic activities are identical in most contexts. The evolutionarily conserved C-terminal binding protein (CtBP) is recruited by a variety of transcription factors that play crucial roles in development and disease. CtBP contains a central NAD(H) binding core domain that is homologous to D2 hydroxy acid dehydrogenase enzymes, as well as an unstructured C-terminal domain. NAD(H) binding is important for CtBP function, but the significance of its intrinsic dehydrogenase activity, as well as that of the unstructured C terminus, is poorly understood. To clarify the biological relevance of these features, we established genetic rescue assays to determine how different forms of CtBP function in the context of Drosophila melanogaster development. The mutant phenotypes and specific gene regulatory effects indicate that both the catalytic site of CtBP and the C-terminal extension play important, if nonessential roles in development. Our results indicate that the structural and enzymatic features of CtBP, previously thought to be dispensable for overall transcriptional control, are critical for modulating this protein's activity in diverse developmental settings.
机译：转录核心加压因子在发育基因调控中起着复杂的作用。这些蛋白质通过募集各种染色质修饰酶来控制转录，但是尚不清楚在不同的发育环境中是否精确调节了核心表达抑制剂的活性，或者在大多数情况下其基本活性是否相同。进化保守的C末端结合蛋白（CtBP）被多种在发育和疾病中起关键作用的转录因子所募集。 CtBP包含与D2羟基酸脱氢酶同源的中央NAD（H）结合核心结构域，以及非结构化的C末端结构域。 NAD（H）绑定对于CtBP功能很重要，但对其内在脱氢酶活性以及非结构化C末端的重要性的了解却很少。为了阐明这些特征的生物学相关性，我们建立了基因拯救试验，以确定在果蝇发展过程中不同形式的CtBP的功能。突变表型和特定的基因调控作用表明，CtBP的催化位点和C末端延伸在发育中起着重要的作用。我们的结果表明，CtBP的结构和酶学特征（以前认为对总体转录控制而言是必不可少的），对于调节这种蛋白质在各种发育环境中的活性至关重要。

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