Chronic Nod2 Stimulation Potentiates Activating Transcription Factor 3 and Paradoxical Superinduction of Epithelial Proinflammatory Chemokines by Mucoactive Ribotoxic Stressors via RNA-Binding Protein Human Antigen R

2011 ◽  
Vol 125 (1) ◽  
pp. 116-125 ◽  
Author(s):  
Seong Hwan Park ◽  
Hye Jin Choi ◽  
Kee Hun Do ◽  
Hyun Yang ◽  
Juil Kim ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Activating Transcription Factor 3 ◽  
Human Antigen R ◽  
Activating Transcription Factor ◽  
Transcription Factor 3

scholarly journals Polyamines Regulate the Stability of Activating Transcription Factor-2 mRNA through RNA-binding Protein HuR in Intestinal Epithelial Cells

2007 ◽  
Vol 18 (11) ◽  
pp. 4579-4590 ◽  
Author(s):  
Lan Xiao ◽  
Jaladanki N. Rao ◽  
Tongtong Zou ◽  
Lan Liu ◽  
Bernard S. Marasa ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Rna Binding ◽  
Binding Protein ◽  
Critical Role ◽  
Rna Binding Protein ◽  
Gene Promoter ◽  
Protein Levels ◽  
Ribonucleoprotein Complexes ◽  
Activating Transcription Factor ◽  
The Stability

Maintenance of intestinal mucosal epithelial integrity requires polyamines that modulate the expression of various genes involved in cell proliferation and apoptosis. Recently, polyamines were shown to regulate the subcellular localization of the RNA-binding protein HuR, which stabilizes its target transcripts such as nucleophosmin and p53 mRNAs. The activating transcription factor-2 (ATF-2) mRNA encodes a member of the ATF/CRE-binding protein family of transcription factors and was computationally predicted to be a target of HuR. Here, we show that polyamines negatively regulate ATF-2 expression posttranscriptionally and that polyamine depletion stabilizes ATF-2 mRNA by enhancing the interaction of the 3′-untranslated region (UTR) of ATF-2 with cytoplasmic HuR. Decreasing cellular polyamines by inhibiting ornithine decarboxylase (ODC) with α-difluoromethylornithine increased the levels of ATF-2 mRNA and protein, whereas increasing polyamines by ectopic ODC overexpression repressed ATF-2 expression. Polyamine depletion did not alter transcription via the ATF-2 gene promoter but increased the stability of ATF-2 mRNA. Increased cytoplasmic HuR in polyamine-deficient cells formed ribonucleoprotein complexes with the endogenous ATF-2 mRNA and specifically bound to 3′-UTR of ATF-2 mRNA on multiple nonoverlapping 3′-UTR segments. Adenovirus-mediated HuR overexpression elevated ATF-2 mRNA and protein levels, whereas HuR silencing rendered the ATF-2 mRNA unstable and prevented increases in ATF-2 mRNA and protein. Furthermore, inhibition of ATF-2 expression prevented the increased resistance of polyamine-deficient cells to apoptosis induced by treatment with tumor necrosis factor-α and cycloheximide. These results indicate that polyamines modulate the stability of ATF-2 mRNA by altering cytoplasmic HuR levels and that polyamine-modulated ATF-2 expression plays a critical role in regulating epithelial apoptosis.

scholarly journals Role of activating transcription factor 3 protein ATF3 in necrosis and apoptosis induced by 5-fluoro-2′-deoxyuridine

FEBS Journal ◽  
2014 ◽  
Vol 281 (7) ◽  
pp. 1892-1900 ◽  
Author(s):  
Akira Sato ◽  
Kentaro Nakama ◽  
Hiroki Watanabe ◽  
Akito Satake ◽  
Akihiro Yamamoto ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Activating Transcription Factor 3 ◽  
Activating Transcription Factor ◽  
Transcription Factor 3
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