Stabilization of urokinase and urokinase receptor mRNAs by HuR is linked to its cytoplasmic accumulation induced by activated mitogen-activated protein kinase-activated protein kinase 2

Details

Serval ID
serval:BIB_7AC2677F0D71
Type
Article: article from journal or magazin.
Collection
Publications
Title
Stabilization of urokinase and urokinase receptor mRNAs by HuR is linked to its cytoplasmic accumulation induced by activated mitogen-activated protein kinase-activated protein kinase 2
Journal
Molecular and Cell Biology
Author(s)
Tran H., Maurer F., Nagamine Y.
ISSN
0270-7306 (Print)
Publication state
Published
Issued date
10/2003
Volume
23
Number
20
Pages
7177-88
Notes
DA - 20030930LA - engPT - Journal ArticleRN - 0 (Antigens, Surface)RN - 0 (ELAV-like protein 1)RN - 0 (Intracellular Signaling Peptides and Proteins)RN - 0 (RNA, Messenger)RN - 0 (RNA-Binding Proteins)RN - 0 (Receptors, Cell Surface)RN - 0 (Recombinant Proteins)RN - 0 (urokinase-type plasminogen activator receptors)RN - 564-25-0 (Doxycycline)RN - 63231-63-0 (RNA)RN - 7722-84-1 (Hydrogen Peroxide)RN - EC 2.5.1.18 (Glutathione Transferase)RN - EC 2.7.1.- (MAP-kinase-activated kinase 2)RN - EC 2.7.1.37 (Mitogen-Activated Protein Kinases)RN - EC 2.7.1.37 (Protein Kinases)RN - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)RN - EC 3.4.21.73 (Urinary Plasminogen Activator)SB - IM --- Old month value: Oct
Abstract
The mRNAs of urokinase plasminogen activator (uPA) and its receptor, uPAR, contain instability-determining AU-rich elements (AREs) in their 3' untranslated regions. The cellular proteins binding to these RNA sequences (ARE(uPA/uPAR)) are not known. We show here that the mRNA-stabilizing factor HuR functionally interacts with these sequences. HuR stabilized an ARE(uPA)-containing RNA substrate in vitro and stabilized in HeLa Tet-off cells both endogenous uPA and uPAR mRNAs and a beta-globin reporter mRNA containing the ARE(uPA). RNAi-mediated depletion of HuR in BT-549 and MDA-MB-231 cells significantly reduced the steady-state levels of endogenous uPA and uPAR mRNAs. Furthermore, we show that a constitutively active form of mitogen-activated protein kinase-activated protein kinase 2 (MK2), MK2-EE, has an ARE-mRNA-stabilizing effect that correlates with its ability to enhance the cytoplasmic accumulation of endogenous HuR, but not in cells cotransfected with a dominant negative version of MK2, MK2-K76R. These effects were mimicked by hydrogen peroxide treatment (oxidative stress), which resulted in the phosphorylation of endogenous MK2. In addition, hydrogen peroxide treatment enhanced the cytoplasmic binding of HuR to the ARE(uPA), which was abrogated in cells transfected with MK2-K76R. These results indicate a role for HuR and MK2 in regulating the expression of uPA and uPAR genes at the posttranscriptional level.
Keywords
0, Antigens, Antigens,Surface, BINDING, Biomedical Research, Blotting,Northern, Blotting,Western, Cell Line, Cell Line,Tumor, Cells, Cytoplasm, Doxycycline, Enzyme Activation, EXPRESSION, GENE, Gene Expression Regulation,Enzymologic, Genes, Genes,Dominant, Genetic Vectors, Glutathione, Glutathione Transferase, Hela Cells, Humans, Hydrogen Peroxide, In Vitro, Intracellular Signaling Peptides and Proteins, KINASE, metabolism, Microscopy,Fluorescence, Mitogen-Activated Protein Kinases, Models,Genetic, Oxidative Stress, Peptides, pharmacology, PHOSPHORYLATION, Precipitin Tests, PROTEIN, Protein Binding, Protein Kinases, PROTEIN-KINASE, Protein-Serine-Threonine Kinases, Proteins, RECEPTOR, Receptors,Cell Surface, Recombinant Proteins, Research, Rna, RNA,Messenger, RNA-Binding Proteins, signal transduction, Stress, Time Factors, Transcription,Genetic, Transfection, Ultraviolet Rays, Urinary Plasminogen Activator
Pubmed
Web of science
Open Access
Yes
Create date
30/01/2008 8:31
Last modification date
20/08/2019 14:36
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