ATF4对于内质网应激诱导的REDD1表达上调是必需且充分的。
ATF4 is necessary and sufficient for ER stress-induced upregulation of REDD1 expression.
作者信息
Whitney Michael L, Jefferson Leonard S, Kimball Scot R
机构信息
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, P.O. Box 850, 500 University Drive, Hershey, PA 17033, USA.
出版信息
Biochem Biophys Res Commun. 2009 Feb 6;379(2):451-5. doi: 10.1016/j.bbrc.2008.12.079. Epub 2008 Dec 27.
In response to a variety of cell stresses, e.g. endoplasmic reticulum (ER) stress, expression of REDD1 (regulated in development and DNA damage responses) is transcriptionally upregulated. However, the mechanism through which ER stress acts to upregulate REDD1 expression is unknown. In the present study, REDD1 expression was found to be upregulated by ER stress in several cell lines. However, in MEF cells lacking the eIF2alpha kinase PERK, ER stress failed to upregulate REDD1 expression, demonstrating that phosphorylation of eIF2alpha was necessary for the effect. Moreover, ER stress led to upregulated expression of the transcription factor ATF4, but in MEF cells lacking ATF4, REDD1 mRNA expression was not increased by ER stress. In contrast, exogenous expression of ATF4 was sufficient to induce REDD1 expression. Overall, the results suggest that REDD1 expression is upregulated during ER stress through a mechanism involving activation of PERK, phosphorylation of eIF2alpha, and increased ATF4 expression.
作为对多种细胞应激（如内质网应激）的反应，REDD1（在发育和DNA损伤反应中受调控）的表达在转录水平上被上调。然而，内质网应激上调REDD1表达的机制尚不清楚。在本研究中，发现内质网应激在几种细胞系中上调了REDD1的表达。然而，在缺乏eIF2α激酶PERK的MEF细胞中，内质网应激未能上调REDD1的表达，这表明eIF2α的磷酸化对于该效应是必需的。此外，内质网应激导致转录因子ATF4的表达上调，但在缺乏ATF4的MEF细胞中，内质网应激并未增加REDD1 mRNA的表达。相反，ATF4的外源性表达足以诱导REDD1的表达。总体而言，结果表明内质网应激期间REDD1的表达通过一种涉及PERK激活、eIF2α磷酸化和ATF4表达增加的机制上调。
Zotero 插件