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哺乳动物神经系统中的诱导型和组成型转录因子:Jun、Fos、Krox以及CREB/ATF蛋白对基因表达的调控

Inducible and constitutive transcription factors in the mammalian nervous system: control of gene expression by Jun, Fos and Krox, and CREB/ATF proteins.

作者信息

Herdegen T, Leah J D

机构信息

Institute of Pharmacology, University of Kiel, Hospitalstrasse 4, 24105, Kiel,

出版信息

Brain Res Brain Res Rev. 1998 Dec;28(3):370-490. doi: 10.1016/s0165-0173(98)00018-6.

Abstract

This article reviews findings up to the end of 1997 about the inducible transcription factors (ITFs) c-Jun, JunB, JunD, c-Fos, FosB, Fra-1, Fra-2, Krox-20 (Egr-2) and Krox-24 (NGFI-A, Egr-1, Zif268); and the constitutive transcription factors (CTFs) CREB, CREM, ATF-2 and SRF as they pertain to gene expression in the mammalian nervous system. In the first part we consider basic facts about the expression and activity of these transcription factors: the organization of the encoding genes and their promoters, the second messenger cascades converging on their regulatory promoter sites, the control of their transcription, the binding to dimeric partners and to specific DNA sequences, their trans-activation potential, and their posttranslational modifications. In the second part we describe the expression and possible roles of these transcription factors in neural tissue: in the quiescent brain, during pre- and postnatal development, following sensory stimulation, nerve transection (axotomy), neurodegeneration and apoptosis, hypoxia-ischemia, generalized and limbic seizures, long-term potentiation and learning, drug dependence and withdrawal, and following stimulation by neurotransmitters, hormones and neurotrophins. We also describe their expression and possible roles in glial cells. Finally, we discuss the relevance of their expression for nervous system functioning under normal and patho-physiological conditions.

摘要

本文综述了截至1997年底有关诱导型转录因子(ITFs)c-Jun、JunB、JunD、c-Fos、FosB、Fra-1、Fra-2、Krox-20(Egr-2)和Krox-24(NGFI-A、Egr-1、Zif268)的研究结果;以及组成型转录因子(CTFs)CREB、CREM、ATF-2和SRF在哺乳动物神经系统基因表达中的相关情况。在第一部分,我们探讨这些转录因子表达和活性的基本事实:编码基因及其启动子的结构、汇聚于其调控启动子位点的第二信使级联反应、它们转录的控制、与二聚体伙伴及特定DNA序列的结合、它们的反式激活潜能以及它们的翻译后修饰。在第二部分,我们描述这些转录因子在神经组织中的表达及可能的作用:在静止的大脑中、在出生前和出生后的发育过程中、感觉刺激后、神经切断(轴突切断术)后、神经退行性变和细胞凋亡时、缺氧缺血时、全身性和边缘性癫痫发作时、长时程增强和学习过程中、药物依赖和戒断时,以及在神经递质、激素和神经营养因子刺激后。我们还描述它们在胶质细胞中的表达及可能的作用。最后,我们讨论它们的表达在正常和病理生理条件下对神经系统功能的相关性。

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