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Mol Biol Cell. 2009 Dec;20(23):4885-98. doi: 10.1091/mbc.E09-07-0550. Epub 2009 Oct 7.

Polyamines regulate c-Myc translation through Chk2-dependent HuR phosphorylation.

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1
Cell 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.

Abstract

All mammalian cells depend on polyamines for normal growth and proliferation, but the exact roles of polyamines at the molecular level remain largely unknown. The RNA-binding protein HuR modulates the stability and translation of many target mRNAs. Here, we show that in rat intestinal epithelial cells (IECs), polyamines enhanced HuR association with the 3'-untranslated region of the c-Myc mRNA by increasing HuR phosphorylation by Chk2, in turn promoting c-Myc translation. Depletion of cellular polyamines inhibited Chk2 and reduced the affinity of HuR for c-Myc mRNA; these effects were completely reversed by addition of the polyamine putrescine or by Chk2 overexpression. In cells with high content of cellular polyamines, HuR silencing or Chk2 silencing reduced c-Myc translation and c-Myc expression levels. Our findings demonstrate that polyamines regulate c-Myc translation in IECs through HuR phosphorylation by Chk2 and provide new insight into the molecular functions of cellular polyamines.

PMID:
19812253
PMCID:
PMC2785732
DOI:
10.1091/mbc.E09-07-0550
[Indexed for MEDLINE]
Free PMC Article
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