Krüppel -like factor 8 is a stress-responsive transcription factor that regulates expression of HuR.
Krüppel -like factor 8 is a stress-responsive transcription factor that regulates expression of HuR.
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DOI：
10.1159/000363019
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Lee BS
中科院分区：
文献类型：
--
作者：
Govindaraju S;Lee BS
HuR 是一种 RNA 结合蛋白，可调节数千个细胞 mRNA 的转录后生命并促进细胞存活。 HuR 表达为两种 mRNA 转录物，受细胞应激的差异调节。本研究的目的是确定促进较长替代形式转录的因素。转录因子对 HuR 表达的影响通过抑制或过度表达这些因子，然后进行竞争性 RT-PCR、凝胶迁移率变化和染色质免疫沉淀来确定。通过竞争性 RT-PCR 和 Western 分析确定转录因子表达模式。在毒胡萝卜素处理的近端小管细胞和缺血大鼠肾脏中测定应激反应。先前描述的 NF-κB 位点和新鉴定的 Sp/KLF 因子结合位点对于长 HuR mRNA 的转录非常重要。 KLF8（而非 Sp1）被证明可以结合该位点并增加 HuR mRNA 水平。培养或天然近曲小管细胞中的细胞应激导致 KLF8 水平快速下降，与长 HuR mRNA 变体的水平相似。这些结果表明，KLF8 可以参与调节 HuR mRNA 的替代形式以及 NF-κB 和其他因子的表达，具体取决于细胞环境。
HuR is an RNA-binding protein that regulates the post-transcriptional life of thousands of cellular mRNAs and promotes cell survival. HuR is expressed as two mRNA transcripts that are differentially regulated by cell stress. The goal of this study is to define factors that promote transcription of the longer alternate form. Effects of transcription factors on HuR expression were determined by inhibition or overexpression of these factors followed by competitive RT-PCR, gel mobility shift, and chromatin immunoprecipitation. Transcription factor expression patterns were identified through competitive RT-PCR and Western analysis. Stress responses were assayed in thapsigargin-treated proximal tubule cells and in ischemic rat kidney. A previously described NF-κB site and a newly identified Sp/KLF factor binding site were shown to be important for transcription of the long HuR mRNA. KLF8, but not Sp1, was shown to bind this site and increase HuR mRNA levels. Cellular stress in cultured or native proximal tubule cells resulted in a rapid decrease of KLF8 levels that paralleled those of the long HuR mRNA variant. These results demonstrate that KLF8 can participate in regulating expression of alternate forms of HuR mRNA along with NF-κB and other factors, depending on cellular contexts.
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DOI：
10.1007/s00432-010-0776-0
发表时间：
2010-08-01
影响因子：
3.6
作者：
Fu, Wei-Jin;Li, Jia-Chu;Zhu, Hong-Guang
通讯作者：
Zhu, Hong-Guang
影响因子：
4.1
作者：
Guo X;Wu Y;Hartley RS
通讯作者：
Hartley RS
影响因子：
5.3
作者：
Galban, Stefanie;Kuwano, Yuki;Gorospe, Myriam
通讯作者：
Gorospe, Myriam
影响因子：
11.1
作者：
Cheng, Henry S.;Sivachandran, Nirojini;Lau, Andrew;Boudreau, Emilie;Zhao, Jimmy L.;Baltimore, David;Delgado-Olguin, Paul;Cybulsky, Myron I.;Fish, Jason E.
通讯作者：
Fish, Jason E.
影响因子：
11.5
作者：
Denkert, C;Weichert, W;Hauptmann, S
通讯作者：
Hauptmann, S