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Polyamines regulate c-Myc translation through Chk2-dependent HuR phosphorylation.
Lan Liu1, Jaladanki N Rao, Tongtong Zou
1Cell Biology Group, Department of Surgery, and Department of Pathology, University of Maryland School of Medicine and Baltimore Veterans Affairs Medical Center, Baltimore, MD 21201, USA.
Molecular Biology of the Cell
|October 9, 2009
Summary
Polyamines regulate cell growth by enhancing the binding of HuR to c-Myc mRNA. This process involves increased HuR phosphorylation by Chk2, promoting c-Myc translation in intestinal cells.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Polyamines are essential for mammalian cell growth and proliferation, but their precise molecular functions are not fully understood.
- The RNA-binding protein HuR plays a critical role in regulating mRNA stability and translation.
- Understanding the interplay between polyamines and RNA-binding proteins like HuR is crucial for deciphering cellular growth regulation.
Purpose of the Study:
- To elucidate the molecular mechanisms by which polyamines regulate gene expression.
- To investigate the role of the RNA-binding protein HuR in polyamine-mediated cellular processes.
- To determine the impact of polyamines on c-Myc mRNA translation in intestinal epithelial cells.
Main Methods:
- Utilized rat intestinal epithelial cells (IECs) to study polyamine effects.
- Investigated HuR-mRNA interactions using association assays.
- Assessed protein phosphorylation status, specifically of HuR by Chk2.
- Employed gene silencing techniques (HuR and Chk2) and polyamine manipulation (depletion and addition).
Main Results:
- Polyamines enhance HuR binding to the 3'-untranslated region of c-Myc mRNA.
- This enhancement is mediated by increased HuR phosphorylation, catalyzed by Chk2.
- Polyamines promote c-Myc translation through the HuR-Chk2 pathway.
- Depletion of polyamines inhibits Chk2 and reduces HuR-c-Myc mRNA affinity, effects reversible by putrescine or Chk2 overexpression.
Conclusions:
- Polyamines regulate c-Myc translation in intestinal epithelial cells via HuR phosphorylation by Chk2.
- This study reveals a novel molecular mechanism for polyamine function in cellular growth and gene regulation.
- Findings provide new insights into the role of polyamines and HuR in controlling c-Myc expression.
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