Roles of the translationally controlled tumour protein (TCTP) and the double-stranded RNA-dependent protein kinase, PKR, in cellular stress responses

被引：0
作者：
U-A Bommer
C Heng
A Perrin
P Dash
S Lobov
A Elia
M J Clemens
机构：
[1] St George's,Division of Basic Medical Sciences
[2] University of London,undefined
[3] 2Current address: Graduate School of Medicine,undefined
[4] University of Wollongong,undefined
[5] New South Wales 2522,undefined
[6] Australia.,undefined
[7] 3Current address: Hammersmith Hospital,undefined
[8] Imperial College Healthcare NHS Trust,undefined
[9] Du Cane Road,undefined
[10] London W12 0HS,undefined
[11] UK.,undefined
[12] 4Current address: INSERM U841-Eq8-Faculté de Médecine,undefined
[13] Créteil 94010,undefined
[14] France.,undefined
[15] 5Current address: School of Biological Sciences,undefined
[16] University of Reading,undefined
[17] Reading RG6 6AJ,undefined
[18] UK.,undefined
[19] 6Current address: School of Biological Sciences,undefined
[20] University of Wollongong,undefined
[21] Wollongong,undefined
[22] New South Wales 2522,undefined
[23] Australia.,undefined
[24] 7Current address: Department of Chemistry and Biochemistry,undefined
[25] School of Life Sciences,undefined
[26] University of Sussex,undefined
[27] Brighton BN1 9QG,undefined
[28] UK.,undefined
来源：
Oncogene | 2010年 / 29卷
关键词：
TCTP; PKR; p53; apoptosis; cell stress;
D O I：
暂无
中图分类号：
学科分类号：
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 eIF2α. 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 eIF2α phosphorylation.
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页码：763 / 773
页数：10
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