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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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3' Untranslated Regions
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Animals
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Antigens, Surface / genetics
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Antigens, Surface / metabolism*
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Base Sequence
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Checkpoint Kinase 2
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ELAV Proteins
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ELAV-Like Protein 1
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Epithelial Cells / cytology
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Epithelial Cells / drug effects
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Epithelial Cells / physiology
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Gene Expression Regulation / drug effects*
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Gene Silencing
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Intestinal Mucosa / cytology
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Molecular Sequence Data
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Phosphorylation
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Point Mutation
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Polyamines / metabolism*
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Polyamines / pharmacology
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Polyribosomes / chemistry
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Polyribosomes / metabolism
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Protein Biosynthesis*
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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Proto-Oncogene Proteins c-myc / genetics
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Proto-Oncogene Proteins c-myc / metabolism*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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RNA-Binding Proteins / genetics
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RNA-Binding Proteins / metabolism*
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Rats
Substances
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3' Untranslated Regions
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Antigens, Surface
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ELAV Proteins
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ELAV-Like Protein 1
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ELAVL1 protein, human
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Polyamines
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Proto-Oncogene Proteins c-myc
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RNA, Messenger
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RNA-Binding Proteins
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Checkpoint Kinase 2
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CHEK2 protein, human
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Chek2 protein, rat
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Protein Serine-Threonine Kinases