Krüppel -Like Factor 8 is a Stress-Responsive Transcription Factor that Regulates Expression of HuR

Abstract

Background/Aims: 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. Methods: 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. Results: 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. Conclusions: 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.

Electroacupuncture Relieves HuR/KLF9-Mediated Inflammation to Enhance Neurological Repair after Spinal Cord Injury

“…In our study, we have also confirmed the regulation of KLF9 mRNA by HuR. Interestingly, it has been proven that KLF8 (another transcription factor of the KLF family) regulates the expression of HuR(Govindaraju and Lee, 2014). Similarly, there may be a regulatory correlation between HuR and KLF9 in SCI, which could provide new insights for the treatment of SCI.Notably, we acknowledge the limitations of the study: (I) The study was specific to binding mRNAs, and onlyKLF9 was verified; thus, validation of other mRNAs is needed.…”

Suppression of epithelial-mesenchymal transition in hepatocellular carcinoma cells by Krüppel-like factor 4

“…First of all, KLF4 is dispensable for early development [ 7 – 9 ]. Moreover, when KLF4 is expressed in adult somatic cells with other Yamanaka factors [ 10 , 11 ], KLF4 has been shown to promote the formation of induced pluripotent stem (IPS) cells [ 12 ]. For example, KLF4 is found to suppress cell proliferation through modulation of p21Waf1/Cip1 [ 13 ].…”

KLF8 Promotes Temozolomide Resistance in Glioma Cells via β-Catenin Activation

“…Krüppel-like factor (KLF) 8 is a member of the KLF family of transcription factors that contain three C2-H2 zinc fingers in the C-terminal DNA-binding domain, a nuclear localization signal, and a distinct N-terminal domain [9,10]. KLF8 is frequently upregulated in several types of cancer, including hepatocellular carcinoma (HCC), renal carcinoma, and breast, ovarian, and gastric cancers, and plays an important role in a wide range of biological processes, including oncogenic transformation, epithelial-to-mesenchymal transition, and DNA damage response as well as cell growth, invasion, and differentiation [11][12][13][14][15].…”