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首页> 外文期刊>Molecular and Cellular Biology >A monomeric derivative of the cellular transcription factor CREB functions as a constitutive activator.
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A monomeric derivative of the cellular transcription factor CREB functions as a constitutive activator.

机译：细胞转录因子CREB的单体衍生物起组成型激活剂的作用。

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The mammalian transcriptional activator CREB binds as a dimer to a broad spectrum of inducible promoters. CREB activity is modulated by several signalling agents (protein kinase A [PKA], Ca2+, and transforming growth factor beta) and via functional interactions with cell-specific transcription factors. In addition, CREB can activate transcription constitutively and repress the activity of several other transcriptional activators. The mechanisms that allow CREB to act in such a malleable manner and the role that CREB dimerization might play in this are poorly understood. To probe the latter issue, we have created monomeric forms of CREB by fusing CREB to the DNA-binding domain of a protein (B-cell specific activator protein [BSAP]) that binds to DNA as a monomer. Remarkably, monomeric CREB acts as a potent, constitutive activator under conditions in which native CREB is inducible by PKA. Thus, CREB contains constitutive activation regions that are unable to function in native CREB. Two glutamine-rich domains that are important for native, PKA-inducible CREB activity are required for the constitutive activity of monomeric CREB. In contrast, two elements within the kinase-inducible domain of CREB are dispensable for constitutive activity. We discuss our results in relation to inducible and constitutive CREB activity and the potential modes of action of other activators that directly interact with CREB.
机译：哺乳动物转录激活因子CREB作为二聚体与广谱的诱导型启动子结合。 CREB的活性受到几种信号传导剂（蛋白激酶A [PKA]，Ca2 +和转化生长因子β）的调节，并通过与细胞特异性转录因子的功能性相互作用来调节。此外，CREB可以组成性激活转录并抑制其他几种转录激活剂的活性。使CREB以这种可塑方式起作用的机制以及CREB二聚化可能在其中发挥的作用还鲜为人知。为了探究后一个问题，我们通过将CREB融合到作为单体与DNA结合的蛋白质（B细胞特异性激活蛋白[BSAP]）的DNA结合结构域中来创建CREB的单体形式。值得注意的是，单体CREB在PKA可诱导天然CREB的条件下充当有效的组成型激活剂。因此，CREB包含不能在天然CREB中起作用的组成型激活区域。对于天然的，PKA诱导的CREB活性很重要的两个富含谷氨酰胺的域是单体CREB的组成活性所必需的。相反，CREB的激酶诱导结构域中的两个元素对于组成型活性是必不可少的。我们讨论与诱导性和组成性CREB活性以及与CREB直接相互作用的其他激活剂的潜在作用方式有关的结果。

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