An interplay between the p38 MAPK pathway and AUBPs regulates c-fos mRNA stability during mitogenic stimulation
Mitogen-activated protein kinase (MAPK) pathways constitute key regulatory elements linking extracellular stimuli to nuclear gene expression. Immediate-early responsive genes (IEGs) of the activator protein 1 (AP-1) family, such as fos, achieve peak expression levels shortly after cells are stimulat...
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todo:paper_02646021_v467_n1_p77_Degese2023-10-03T15:13:04Z An interplay between the p38 MAPK pathway and AUBPs regulates c-fos mRNA stability during mitogenic stimulation Degese, M.S. Tanos, T. Naipauer, J. Gingerich, T. Chiappe, D. Echeverria, P. LaMarre, J. Gutkind, J.S. Coso, O.A. AUBPs. C-fos P38 MAPKs Stability of mRNAs acidic leucine rich nuclear phosphoprotein 32 family member B AU rich binding protein binding protein far upstream element binding protein 2 Hu antigen Hu antigen R messenger RNA mitogen activated protein kinase p38 phosphoprotein phosphoprotein phosphatase 2 protein c fos unclassified drug 3' untranslated region ELAVL1 protein, human Hu antigen hybrid protein KHSRP protein, human KSRP protein, mouse messenger RNA mitogen activated protein kinase p38 mitogenic agent protein c fos protein kinase inhibitor RNA binding protein transactivator protein 3' untranslated region Article cell proliferation controlled study embryo enzyme activity epithelium cell fibroblast gene overexpression human human cell mitogenesis priority journal protein function protein phosphorylation protein protein interaction protein RNA binding RNA stability 3T3 cell line animal chemistry comparative study drug effects genetics HEK293 cell line HeLa cell line metabolism mouse mutation phosphorylation protein processing RNA stability signal transduction 3' Untranslated Regions Animals Cell Proliferation HEK293 Cells HeLa Cells Hu Paraneoplastic Encephalomyelitis Antigens Humans MAP Kinase Signaling System Mice Mitogens Mutation NIH 3T3 Cells p38 Mitogen-Activated Protein Kinases Phosphorylation Protein Kinase Inhibitors Protein Processing, Post-Translational Proto-Oncogene Proteins c-fos Recombinant Fusion Proteins RNA Stability RNA, Messenger RNA-Binding Proteins Trans-Activators Mitogen-activated protein kinase (MAPK) pathways constitute key regulatory elements linking extracellular stimuli to nuclear gene expression. Immediate-early responsive genes (IEGs) of the activator protein 1 (AP-1) family, such as fos, achieve peak expression levels shortly after cells are stimulated with growth factors and sharply decrease thereafter. Several AU-rich binding proteins (AUBPs), including HuR (Hu-antigen R, Elavlike protein 1, ELAVL1) and KSRP (far upstream element-binding protein 2, KHSRP) bind to a fos AU-rich element (ARE) present in the 3′-UTR (untranslated region) of fos mRNA regulating its stability by a still poorly defined mechanism. We show in the present study that, whereas HuR binds and stabilizes transcribed reporter mRNAs bearing the fos 3′-UTR, KSRP counteracts this effect. Furthermore, we found that fos mRNA stability and HuR phosphorylation status are dependent on the activity of p38 MAPK in both epithelial cells and fibroblasts upon proliferative stimulation. Analysing PPI (protein-protein interaction) networks, we performed a thorough query of interacting proteins for p38 MAPKs, HuR and other AUBPs upon growth factor stimulation. This revealed novel HuR interactors including inhibitors of protein phosphatase 2 (PP2A) activity. Over-expression of two of these interactors, pp32 and APRIL (acidic leucine-rich nuclear phosphoprotein 32 family member B, ANP32B) and pharmacological inhibition of PP2A stabilized a fos reporter mRNA. Our results indicate that p38 MAPK regulates fos mRNA decay by affecting the state of phosphorylation of HuR while controlling yet to be fully elucidated PP regulatory networks. © The Authors Journal compilation © 2015 Biochemical Society. Fil:Degese, M.S. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Tanos, T. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Echeverria, P. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Coso, O.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_02646021_v467_n1_p77_Degese |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
AUBPs. C-fos P38 MAPKs Stability of mRNAs acidic leucine rich nuclear phosphoprotein 32 family member B AU rich binding protein binding protein far upstream element binding protein 2 Hu antigen Hu antigen R messenger RNA mitogen activated protein kinase p38 phosphoprotein phosphoprotein phosphatase 2 protein c fos unclassified drug 3' untranslated region ELAVL1 protein, human Hu antigen hybrid protein KHSRP protein, human KSRP protein, mouse messenger RNA mitogen activated protein kinase p38 mitogenic agent protein c fos protein kinase inhibitor RNA binding protein transactivator protein 3' untranslated region Article cell proliferation controlled study embryo enzyme activity epithelium cell fibroblast gene overexpression human human cell mitogenesis priority journal protein function protein phosphorylation protein protein interaction protein RNA binding RNA stability 3T3 cell line animal chemistry comparative study drug effects genetics HEK293 cell line HeLa cell line metabolism mouse mutation phosphorylation protein processing RNA stability signal transduction 3' Untranslated Regions Animals Cell Proliferation HEK293 Cells HeLa Cells Hu Paraneoplastic Encephalomyelitis Antigens Humans MAP Kinase Signaling System Mice Mitogens Mutation NIH 3T3 Cells p38 Mitogen-Activated Protein Kinases Phosphorylation Protein Kinase Inhibitors Protein Processing, Post-Translational Proto-Oncogene Proteins c-fos Recombinant Fusion Proteins RNA Stability RNA, Messenger RNA-Binding Proteins Trans-Activators |
| spellingShingle |
AUBPs. C-fos P38 MAPKs Stability of mRNAs acidic leucine rich nuclear phosphoprotein 32 family member B AU rich binding protein binding protein far upstream element binding protein 2 Hu antigen Hu antigen R messenger RNA mitogen activated protein kinase p38 phosphoprotein phosphoprotein phosphatase 2 protein c fos unclassified drug 3' untranslated region ELAVL1 protein, human Hu antigen hybrid protein KHSRP protein, human KSRP protein, mouse messenger RNA mitogen activated protein kinase p38 mitogenic agent protein c fos protein kinase inhibitor RNA binding protein transactivator protein 3' untranslated region Article cell proliferation controlled study embryo enzyme activity epithelium cell fibroblast gene overexpression human human cell mitogenesis priority journal protein function protein phosphorylation protein protein interaction protein RNA binding RNA stability 3T3 cell line animal chemistry comparative study drug effects genetics HEK293 cell line HeLa cell line metabolism mouse mutation phosphorylation protein processing RNA stability signal transduction 3' Untranslated Regions Animals Cell Proliferation HEK293 Cells HeLa Cells Hu Paraneoplastic Encephalomyelitis Antigens Humans MAP Kinase Signaling System Mice Mitogens Mutation NIH 3T3 Cells p38 Mitogen-Activated Protein Kinases Phosphorylation Protein Kinase Inhibitors Protein Processing, Post-Translational Proto-Oncogene Proteins c-fos Recombinant Fusion Proteins RNA Stability RNA, Messenger RNA-Binding Proteins Trans-Activators Degese, M.S. Tanos, T. Naipauer, J. Gingerich, T. Chiappe, D. Echeverria, P. LaMarre, J. Gutkind, J.S. Coso, O.A. An interplay between the p38 MAPK pathway and AUBPs regulates c-fos mRNA stability during mitogenic stimulation |
| topic_facet |
AUBPs. C-fos P38 MAPKs Stability of mRNAs acidic leucine rich nuclear phosphoprotein 32 family member B AU rich binding protein binding protein far upstream element binding protein 2 Hu antigen Hu antigen R messenger RNA mitogen activated protein kinase p38 phosphoprotein phosphoprotein phosphatase 2 protein c fos unclassified drug 3' untranslated region ELAVL1 protein, human Hu antigen hybrid protein KHSRP protein, human KSRP protein, mouse messenger RNA mitogen activated protein kinase p38 mitogenic agent protein c fos protein kinase inhibitor RNA binding protein transactivator protein 3' untranslated region Article cell proliferation controlled study embryo enzyme activity epithelium cell fibroblast gene overexpression human human cell mitogenesis priority journal protein function protein phosphorylation protein protein interaction protein RNA binding RNA stability 3T3 cell line animal chemistry comparative study drug effects genetics HEK293 cell line HeLa cell line metabolism mouse mutation phosphorylation protein processing RNA stability signal transduction 3' Untranslated Regions Animals Cell Proliferation HEK293 Cells HeLa Cells Hu Paraneoplastic Encephalomyelitis Antigens Humans MAP Kinase Signaling System Mice Mitogens Mutation NIH 3T3 Cells p38 Mitogen-Activated Protein Kinases Phosphorylation Protein Kinase Inhibitors Protein Processing, Post-Translational Proto-Oncogene Proteins c-fos Recombinant Fusion Proteins RNA Stability RNA, Messenger RNA-Binding Proteins Trans-Activators |
| description |
Mitogen-activated protein kinase (MAPK) pathways constitute key regulatory elements linking extracellular stimuli to nuclear gene expression. Immediate-early responsive genes (IEGs) of the activator protein 1 (AP-1) family, such as fos, achieve peak expression levels shortly after cells are stimulated with growth factors and sharply decrease thereafter. Several AU-rich binding proteins (AUBPs), including HuR (Hu-antigen R, Elavlike protein 1, ELAVL1) and KSRP (far upstream element-binding protein 2, KHSRP) bind to a fos AU-rich element (ARE) present in the 3′-UTR (untranslated region) of fos mRNA regulating its stability by a still poorly defined mechanism. We show in the present study that, whereas HuR binds and stabilizes transcribed reporter mRNAs bearing the fos 3′-UTR, KSRP counteracts this effect. Furthermore, we found that fos mRNA stability and HuR phosphorylation status are dependent on the activity of p38 MAPK in both epithelial cells and fibroblasts upon proliferative stimulation. Analysing PPI (protein-protein interaction) networks, we performed a thorough query of interacting proteins for p38 MAPKs, HuR and other AUBPs upon growth factor stimulation. This revealed novel HuR interactors including inhibitors of protein phosphatase 2 (PP2A) activity. Over-expression of two of these interactors, pp32 and APRIL (acidic leucine-rich nuclear phosphoprotein 32 family member B, ANP32B) and pharmacological inhibition of PP2A stabilized a fos reporter mRNA. Our results indicate that p38 MAPK regulates fos mRNA decay by affecting the state of phosphorylation of HuR while controlling yet to be fully elucidated PP regulatory networks. © The Authors Journal compilation © 2015 Biochemical Society. |
| format |
JOUR |
| author |
Degese, M.S. Tanos, T. Naipauer, J. Gingerich, T. Chiappe, D. Echeverria, P. LaMarre, J. Gutkind, J.S. Coso, O.A. |
| author_facet |
Degese, M.S. Tanos, T. Naipauer, J. Gingerich, T. Chiappe, D. Echeverria, P. LaMarre, J. Gutkind, J.S. Coso, O.A. |
| author_sort |
Degese, M.S. |
| title |
An interplay between the p38 MAPK pathway and AUBPs regulates c-fos mRNA stability during mitogenic stimulation |
| title_short |
An interplay between the p38 MAPK pathway and AUBPs regulates c-fos mRNA stability during mitogenic stimulation |
| title_full |
An interplay between the p38 MAPK pathway and AUBPs regulates c-fos mRNA stability during mitogenic stimulation |
| title_fullStr |
An interplay between the p38 MAPK pathway and AUBPs regulates c-fos mRNA stability during mitogenic stimulation |
| title_full_unstemmed |
An interplay between the p38 MAPK pathway and AUBPs regulates c-fos mRNA stability during mitogenic stimulation |
| title_sort |
interplay between the p38 mapk pathway and aubps regulates c-fos mrna stability during mitogenic stimulation |
| url |
http://hdl.handle.net/20.500.12110/paper_02646021_v467_n1_p77_Degese |
| work_keys_str_mv |
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