QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 20, Issue 23, 4885-4898, December 1, 2009

This Article Full Text Full Text (PDF) Supplemental Materials All Versions of this Article: E09-07-0550v1 20/23/4885    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liu, L. Articles by Wang, J.-Y. Search for Related Content PubMed PubMed Citation Articles by Liu, L. Articles by Wang, J.-Y.

Polyamines Regulate c-Myc Translation through Chk2-dependent HuR Phosphorylation

Lan Liu^*,, Jaladanki N. Rao^*,, Tongtong Zou^*,, Lan Xiao^*,, Peng-Yuan Wang^*,, Douglas J. Turner^*,, Myriam Gorospe, and Jian-Ying Wang^*,,

*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; and Laboratory of Cellular and Molecular Biology, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, MD 21224

Submitted July 6, 2009; Revised September 3, 2009; Accepted September 30, 2009
Monitoring Editor: William P. Tansey

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.

Address correspondence to: Jian-Ying Wang (jwang{at}smail.umaryland.edu).

This article has been cited by other articles:

				L. Xiao, J. N. Rao, T. Zou, L. Liu, T. X. Yu, X. Y. Zhu, J. M. Donahue, and J. Y. Wang Induced ATF-2 represses CDK4 transcription through dimerization with JunD inhibiting intestinal epithelial cell growth after polyamine depletion Am J Physiol Cell Physiol, May 1, 2010; 298(5): C1226 - C1234. [Abstract] [Full Text] [PDF]