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 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.
Liu
Lan
L
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.
Rao
Jaladanki N
JN
Zou
Tongtong
T
Xiao
Lan
L
Wang
Peng-Yuan
PY
Turner
Douglas J
DJ
Gorospe
Myriam
M
Wang
Jian-Ying
JY
D020413:3' Untranslated Regions; D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D064447:Checkpoint Kinase 2; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects*; D020868:Gene Silencing; D007413:Intestinal Mucosa / Q000166:cytology; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017354:Point Mutation; D011073:Polyamines / Q000378:metabolism* / Q000494:pharmacology; D011132:Polyribosomes / Q000737:chemistry / Q000378:metabolism; D014176:Protein Biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats
D020413:3' Untranslated Regions; D000954:Antigens, Surface; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D011073:Polyamines; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; C578632:Chek2 protein, rat; D017346:Protein Serine-Threonine Kinases