The Transcription Factor Network Associated With the Amino Acid Response in Mammalian Cells
The Transcription Factor Network Associated With the Amino Acid Response in Mammalian Cells
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DOI：
10.3945/an.112.001891
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发表时间：
2012-05-01
影响因子：
9.3
通讯作者：
Shan, Jixiu
中科院分区：
文献类型：
--
作者：
Kilberg, Michael S.;Balasubramanian, Mukundh;Shan, Jixiu
哺乳动物表现出多种适应机制，可以感知和响应饮食营养的波动。摄入较少的总蛋白质或缺乏一种或多种必需氨基酸的蛋白质饮食会引发摄食行为和基因表达的广泛变化。在单个细胞水平上，膳食蛋白质缺乏表现为氨基酸(AA)缺乏，激活AA反应(AAR)。AAR由一组信号转导通路组成，这些信号转导通路终止于特定的转录程序，旨在催化对营养胁迫的适应，或最终经历细胞凋亡。内质网应激独立于AAR，激活3条信号通路，统称为未折叠蛋白反应。激活转录因子4的转录因子是AAR和未折叠蛋白反应的末端转录调节因子之一，导致这些应激途径的靶基因有很大程度的重叠。在过去的5年里，研究发现碱性亮氨酸拉链超家族转录因子在AAR中起着核心作用。激活转录因子、CCAAT增强子结合蛋白和Fos/Jun碱性亮氨酸拉链蛋白家族之间形成的同源和异源二聚体构成了高度整合的转录因子网络的核心，该网络决定了细胞对饮食蛋白或AA限制的反应的启动、幅度和持续时间。纳特上将。2012年3：295-306。
Mammals exhibit multiple adaptive mechanisms that sense and respond to fluctuations in dietary nutrients. Consumption of reduced total dietary protein or a protein diet that is deficient in 1 or more of the essential amino acids triggers wide-ranging changes in feeding behavior and gene expression. At the level of individual cells, dietary protein deficiency is manifested as amino acid (AA) deprivation, which activates the AA response (AAR). The AAR is composed of a collection of signal transduction pathways that terminate in specific transcriptional programs designed to catalyze adaptation to the nutrient stress or, ultimately, undergo apoptosis. Independently of the AAR, endoplasmic reticulum stress activates 3 signaling pathways, collectively referred to as the unfolded protein response. The transcription factor activating transcription factor 4 is one of the terminal transcriptional mediators for both the AAR and the unfolded protein response, leading to a significant degree of overlap with regard to the target genes for these stress pathways. Over the past 5 y, research has revealed that the basic leucine zipper superfamily of transcription factors plays the central role in the AAR. Formation of both homo- and heterodimers among the activating transcription factor, CCAAT enhancer-binding protein, and FOS/JUN families of basic leucine zipper proteins forms the nucleus of a highly integrated transcription factor network that determines the initiation, magnitude, and duration of the cellular response to dietary protein or AA limitation. Adv. Nutr. 3: 295-306, 2012.