Interleukin-4-induced posttranscriptional gene regulation of CCL26 by the RNA-binding protein HuR in primary human nasal polyp-derived epithelial cells

2018 ◽  
Vol 9 (3) ◽  
pp. 311-321 ◽  
Author(s):  
Peng Tian ◽  
Huashuang Ou ◽  
Fan Wu ◽  
Yun Ma ◽  
Xiang Liu ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Epithelial Cells ◽  
Nasal Polyp ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Interleukin 4 ◽  
Posttranscriptional Gene Regulation

scholarly journals Transcriptional regulation of importin-α1 by JunD modulates subcellular localization of RNA-binding protein HuR in intestinal epithelial cells

2016 ◽  
Vol 311 (6) ◽  
pp. C874-C883 ◽  
Author(s):  
Yan Xu ◽  
Jie Chen ◽  
Lan Xiao ◽  
Hee Kyoung Chung ◽  
Yuan Zhang ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Subcellular Localization ◽  
Rna Binding ◽  
Nuclear Translocation ◽  
Intestinal Epithelial Cells ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Intestinal Epithelial ◽  
Mucosal Regeneration ◽  
Importin Α

The RNA-binding protein HuR is crucial for normal intestinal mucosal regeneration by modulating the stability and translation of target mRNAs, but the exact mechanism underlying HuR trafficking between the cytoplasm and nucleus remains largely unknown. Here we report a novel function of transcription factor JunD in the regulation of HuR subcellular localization through the control of importin-α1 expression in intestinal epithelial cells (IECs). Ectopically expressed JunD specifically inhibited importin-α1 at the transcription level, and this repression is mediated via interaction with CREB-binding site that was located at the proximal region of importin-α1 promoter. Reduction in the levels of importin-α1 by JunD increased cytoplasmic levels of HuR, although it failed to alter whole cell HuR levels. Increased levels of endogenous JunD by depleting cellular polyamines also inhibited importin-α1 expression and increased cytoplasmic HuR levels, whereas JunD silencing rescued importin-α1 expression and enhanced HuR nuclear translocation in polyamine-deficient cells. Moreover, importin-α1 silencing protected IECs against apoptosis, which was prevented by HuR silencing. These results indicate that JunD regulates HuR subcellular distribution by downregulating importin-α1, thus contributing to the maintenance of gut epithelium homeostasis.

scholarly journals Role of the RNA-Binding Protein Tristetraprolin in Glucocorticoid-Mediated Gene Regulation

2008 ◽  
Vol 180 (12) ◽  
pp. 8342-8353 ◽  
Author(s):  
Faoud T. Ishmael ◽  
Xi Fang ◽  
Maria Rosaria Galdiero ◽  
Ulus Atasoy ◽  
William F. C. Rigby ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein

The RNA-binding protein HuR stabilizes survivin mRNA in human oesophageal epithelial cells

2011 ◽  
Vol 437 (1) ◽  
pp. 89-96 ◽  
Author(s):  
James M. Donahue ◽  
Elizabeth T. Chang ◽  
Lan Xiao ◽  
Peng-Yuan Wang ◽  
Jaladanki N. Rao ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Oesophageal Cancer ◽  
Mrna Stability ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Survivin Expression ◽  
Transcriptional Level ◽  
Survivin Mrna ◽  
Hu Antigen R

Overexpression of survivin, a member of the IAP (inhibitor of apoptosis) family, has been correlated with poorer outcomes in multiple malignancies, including oesophageal cancer. The regulatory mechanisms, particularly at the post-transcriptional level, involved in survivin overexpression are not well understood. Previous work from our group has shown that the RNA-binding protein HuR (Hu antigen R), which is also overexpressed in several malignancies, stabilizes the mRNA of XIAP (X-linked IAP), another IAP family member. In the present study, we demonstrate the binding of HuR to a 288 bp fragment in the 3′-UTR (untranslated region) of survivin mRNA in human oesophageal epithelial cells. Unexpectedly, overexpression of HuR led to a decrease in survivin expression. This was associated with decreased survivin mRNA and promoter activity, suggesting a decrease in transcription. Levels of p53, a negative transcriptional regulator of survivin, increased following HuR overexpression, in conjunction with enhanced p53 mRNA stability. Silencing p53 prior to HuR overexpression resulted in increased survivin protein and mRNA stability. These results demonstrate that, in the absence of p53, HuR overexpression results in increased survivin mRNA stability and protein expression. This provides an additional explanation for the increased survivin expression observed in oesophageal cancer cells that have lost p53.

scholarly journals Novel intestinal splice variants of RNA-binding protein CUGBP2: isoform-specific effects on mitotic catastrophe

2008 ◽  
Vol 294 (4) ◽  
pp. G971-G981 ◽  
Author(s):  
Satish Ramalingam ◽  
Gopalan Natarajan ◽  
Chris Schafer ◽  
Dharmalingam Subramaniam ◽  
Randal May ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Rna Binding ◽  
Intestinal Epithelial Cells ◽  
Splice Variants ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Cyclin B1 ◽  
Mitotic Catastrophe ◽  
Intestinal Epithelial ◽  
Cox 2

CUG triplet repeat-binding protein 2 (CUGBP2) is a RNA-binding protein that regulates mRNA translation and modulates apoptosis. Here, we report the identification of two splice variants (termed variants 2 and 3) in cultured human intestinal epithelial cells and in mouse gastrointestinal tract. The variants are generated from alternative upstream promoters resulting in the inclusion of additional NH2-terminal residues. Although variant 2 is the predominant isoform in normal intestine, its expression is reduced, whereas variant 1 is overexpressed following γ-irradiation. All three variants bind cyclooxygenase-2 (COX-2) mRNA. However, only variant 1 inhibits the translation of the endogenous COX-2 mRNA and a chimeric luciferase mRNA containing the COX-2 3′untranslated region. Furthermore, whereas variant 1 is predominantly nuclear, variants 2 and 3 are predominantly cytoplasmic. These data imply that the additional amino acids affect CUGBP2 function. Previous studies have demonstrated that variant 1 induces intestinal epithelial cells to undergo apoptosis. However, in contrast to variant 1, the two novel variants do not affect proliferation or apoptosis of HCT116 cells. In addition, only variant 1 induced G2/M cell cycle arrest, which was overcome by prostaglandin E2. Moreover, variant 1 increased cellular levels of phosphorylated p53 and Bax and decreased Bcl2. Caspase-3 and -9 were also activated, suggesting the initiation of the intrinsic apoptotic pathway. Furthermore, increased phosphorylation of checkpoint kinase (Chk)1 and Chk2 kinases and increased nuclear localization of Cdc2 and cyclin B1 suggested that cells were in mitotic transition. Taken together, these data demonstrate that cells expressing CUGBP2 variant 1 undergo apoptosis during mitosis, suggesting mitotic catastrophe.

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