生物
蛋白激酶R
细胞生物学
EIF-2激酶
蛋白激酶A
激酶
下调和上调
细胞凋亡
细胞应激反应
磷酸化
衣霉素
未折叠蛋白反应
细胞周期蛋白依赖激酶2
生物化学
内质网
战斗或逃跑反应
基因
作者
Ulrich-Axel Bommer,Cheryl Heng,Aline Perrin,Philip R. Dash,Sergei Lobov,Androulla Elia,Michael J. Clemens
出处
期刊:Oncogene
[Springer Nature]
日期:2010-02-04
卷期号:29 (5): 763-773
被引量:38
摘要
Translationally controlled tumour protein (TCTP) is a highly conserved protein present in all eukaryotic organisms. Various cellular functions and molecular interactions have been ascribed to this protein, many related to its growth-promoting and antiapoptotic properties. TCTP levels are highly regulated in response to various cellular stimuli and stresses. We have shown recently that the double-stranded RNA-dependent protein kinase, PKR, is involved in translational regulation of TCTP. Here we extend these studies by demonstrating that TCTP is downregulated in response to various proapoptotic treatments, in particular agents that induce Ca(++) stress, in a PKR-dependent manner. This regulation requires phosphorylation of protein synthesis factor eIF2alpha. Since TCTP has been characterized as an antiapoptotic and Ca(++)-binding protein, we asked whether it is involved in protecting cells from Ca(++)-stress-induced apoptosis. Overexpression of TCTP partially protects cells against thapsigargin-induced apoptosis, as measured using caspase-3 activation assays, a nuclear fragmentation assay, using fluorescence-activated cell sorting analysis, and time-lapse video microscopy. TCTP also protects cells against the proapoptotic effects of tunicamycin and etoposide, but not against those of arsenite. Our results imply that cellular TCTP levels influence sensitivity to apoptosis and that PKR may exert its proapoptotic effects at least in part through downregulation of TCTP via eIF2alpha phosphorylation.
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