ATF4 is necessary and sufficient for ER stress-induced upregulation of REDD1 expression.
ATF4 is necessary and sufficient for ER stress-induced upregulation of REDD1 expression.
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DOI：
10.1016/j.bbrc.2008.12.079
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发表时间：
2009-02-06
影响因子：
3.1
通讯作者：
Kimball, Scot R.
中科院分区：
文献类型：
--
作者：
Whitney, Michael L.;Jefferson, Leonard S.;Kimball, Scot R.
响应于多种细胞应激，例如内质网（ER）应激，REDD 1的表达（在发育和DNA损伤反应中调节）在转录上上调。然而，ER应激上调REDD1表达的机制尚不清楚。在本研究中，REDD1的表达被发现在几种细胞系中被ER应激上调。然而，在缺乏eIF2α激酶PERK的MEF细胞中，ER应激未能上调REDD 1表达，表明eIF2α的磷酸化是该效应所必需的。此外，ER应激导致转录因子ATF4的表达上调，但在缺乏ATF4的MEF细胞中，REDD1 mRNA的表达并不因ER应激而增加。相反，ATF4的外源性表达足以诱导REDD1表达。总体而言，结果表明，在ER应激期间，REDD1表达通过涉及PERK激活、eIF2α磷酸化和ATF 4表达增加的机制上调。
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 eIF2α kinase PERK, ER stress failed to upregulate REDD1 expression, demonstrating that phosphorylation of eIF2α 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 eIF2α, and increased ATF4 expression.
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影响因子：
16
作者：
Harding, HP;Novoa, I;Ron, D
通讯作者：
Ron, D
影响因子：
9.2
作者：
Long, X;Lin, Y;Avruch, J
通讯作者：
Avruch, J
影响因子：
6.4
作者：
Protiva, Petr;Hopkins, Michael E.;Bernard, Weinstein I.
通讯作者：
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影响因子：
4.8
作者：
Thiaville, Michelle M.;Pan, Yuan-Xiang;Kilberg, Michael S.
通讯作者：
Kilberg, Michael S.
DOI：
10.1083/jcb.153.5.1011
发表时间：
2001-05-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Novoa I;Zeng H;Harding HP;Ron D
通讯作者：
Ron D