Human CCAAT/enhancer-binding protein β gene expression is activated by endoplasmic reticulum stress through an unfolded protein response element downstream of the protein coding sequence

被引:55
作者
Chen, C
Dudenhausen, EE
Pan, YX
Zhong, C
Kilberg, MS
机构
[1] Univ Florida, Coll Med, Ctr Mammalian Genet, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA
[2] Univ Florida, Coll Med, Ctr Nutr Sci, Gainesville, FL 32610 USA
关键词
D O I
10.1074/jbc.M313920200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
CCAAT/enhancer-binding protein beta (C/EBPbeta) is a member of the bZIP family of transcription factors that contribute to the regulation of a wide range of important cellular processes. The data in the present study document that transcription from the human C/EBPbeta gene is induced in response to endoplasmic reticulum stress, such as glucose deprivation, or treatment of cells with tunicamycin or thapsigargin. Transient transfection of C/EBPbeta genomic fragments linked to a luciferase reporter gene demonstrated that the C/EBPbeta promoter plays no major regulatory role. Instead, by deletion analysis it was discovered that a 46-bp region, located at a genomic site that corresponds to the 3'-untranslated region of the C/EBPbeta mRNA, harbored an element that was required for the stress response. Mutagenesis demonstrated that a cis-regulatory element located at nt + 1614 - 1621 (5'-TGACGCAA-3') is responsible for activation of the C/EBPbeta gene. Electrophoresis mobility shift analysis revealed that proteins are bound to this element and that the amount of binding is increased following glucose deprivation. This element is homologous to a previously reported mammalian unfolded protein response element that binds XBP-1. Consistent with those data, overexpression of XBP-1 caused an increase in transcription that was mediated by the C/EBPbeta mammalian unfolded protein response element.
引用
收藏
页码:27948 / 27956
页数:9
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