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

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 cel...

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Bibliographic Details
Published in:Molecular biology of the cell 2009-12, Vol.20 (23), p.4885-4898
Main Authors: Liu, Lan, Rao, Jaladanki N, Zou, Tongtong, Xiao, Lan, Wang, Peng-Yuan, Turner, Douglas J, Gorospe, Myriam, Wang, Jian-Ying
Format: Article
Language:English
Subjects:
3' Untranslated Regions
Animals
Antigens, Surface - genetics
Antigens, Surface - metabolism
Base Sequence
Checkpoint Kinase 2
ELAV Proteins
ELAV-Like Protein 1
Epithelial Cells - cytology
Epithelial Cells - drug effects
Epithelial Cells - physiology
Gene Expression Regulation - drug effects
Gene Silencing
Intestinal Mucosa - cytology
Molecular Sequence Data
Phosphorylation
Point Mutation
Polyamines - metabolism
Polyamines - pharmacology
Polyribosomes - chemistry
Polyribosomes - metabolism
Protein Biosynthesis
Protein-Serine-Threonine Kinases - genetics
Protein-Serine-Threonine Kinases - metabolism
Proto-Oncogene Proteins c-myc - genetics
Proto-Oncogene Proteins c-myc - metabolism
Rats
RNA, Messenger - genetics
RNA, Messenger - metabolism
RNA-Binding Proteins - genetics
RNA-Binding Proteins - metabolism
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Summary: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.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.E09-07-0550