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The Notch intracellular domain represses CRE-dependent transcription

机译：Notch细胞内结构域抑制CRE依赖性转录

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摘要

Members of the cyclic-AMP response-element binding protein (CREB) transcription factor family regulate the expression of genes needed for long-term memory formation. Loss of Notch impairs long-term, but not short-term, memory in flies and mammals. We investigated if the Notch-1 (N1) exerts an effect on CREB-dependent gene transcription. We observed that N1 inhibits CREB mediated activation of cyclic-AMP response element (CRE) containing promoters in a gamma-secretase-dependent manner. We went on to find that the gamma-cleaved N1 intracellular domain (N1ICD) sequesters nuclear CREB1 alpha, inhibits cAMP/PKA-mediated neurite outgrowth and represses the expression of specific CREB regulated genes associated with learning and memory in primary cortical neurons. Similar transcriptional effects were observed with the N2ICD, N3ICD and N4ICDs. Together, these observations indicate that the effects of Notch on learning and memory are, at least in part, via an effect on CREB-regulated gene expression. (C) 2014 The Authors. Published by Elsevier Inc This is an open access article under the CC BY-NC-ND license.
机译：环状AMP应答元件结合蛋白（CREB）转录因子家族的成员调节长期记忆形成所需的基因表达。 Notch的丧失会损害果蝇和哺乳动物的长期记忆，而不是短期记忆。我们调查了Notch-1（N1）是否对CREB依赖性基因转录产生影响。我们观察到，N1以γ-分泌酶依赖性方式抑制CREB介导的包含启动子的环状AMP反应元件（CRE）的激活。我们继续发现，γ切割的N1细胞内结构域（N1ICD）隔离核CREB1α，抑制cAMP / PKA介导的神经突增生，并抑制与原代皮层神经元的学习和记忆相关的特定CREB调控基因的表达。用N2ICD，N3ICD和N4ICD观察到类似的转录作用。总之，这些观察结果表明，Notch对学习和记忆的影响至少部分是通过对CREB调节的基因表达的影响。 （C）2014作者。由Elsevier Inc发布这是CC BY-NC-ND许可下的开放获取文章。

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