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" (2015) Biochemical Journal. 467(1):77-90
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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.


Documento: Artículo
Título:An interplay between the p38 MAPK pathway and AUBPs regulates c-fos mRNA stability during mitogenic stimulation
Autor:Degese, M.S.; Tanos, T.; Naipauer, J.; Gingerich, T.; Chiappe, D.; Echeverria, P.; LaMarre, J.; Gutkind, J.S.; Coso, O.A.
Filiación:LFBM-DFBMC, Departamento de Fisiología Y Biología Molecular, Universidad de Buenos Aires (FCEN-UBA), Buenos Aires, C1428EHA, Argentina
IFIBYNE-CONICET, Buenos Aires, C1428EHA, Argentina
DBMS, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada
Proteomics Core Facility, École Polytechnique Fédérale de Lausanne, Lausanne, CH-1015, Switzerland
Département de Biologie Cellulaire, Université de Genève, Sciences 3, Genève 4, CH-1211, Switzerland
Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD 20892-4330, United States
Palabras clave: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
Página de inicio:77
Página de fin:90
Título revista:Biochemical Journal
Título revista abreviado:Biochem. J.
CAS:3' Untranslated Regions; ELAVL1 protein, human; Hu Paraneoplastic Encephalomyelitis Antigens; KHSRP protein, human; KSRP protein, mouse; Mitogens; p38 Mitogen-Activated Protein Kinases; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-fos; Recombinant Fusion Proteins; RNA, Messenger; RNA-Binding Proteins; Trans-Activators


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---------- APA ----------
Degese, M.S., Tanos, T., Naipauer, J., Gingerich, T., Chiappe, D., Echeverria, P., LaMarre, J.,..., Coso, O.A. (2015) . An interplay between the p38 MAPK pathway and AUBPs regulates c-fos mRNA stability during mitogenic stimulation. Biochemical Journal, 467(1), 77-90.
---------- CHICAGO ----------
Degese, M.S., Tanos, T., Naipauer, J., Gingerich, T., Chiappe, D., Echeverria, P., et al. "An interplay between the p38 MAPK pathway and AUBPs regulates c-fos mRNA stability during mitogenic stimulation" . Biochemical Journal 467, no. 1 (2015) : 77-90.
---------- MLA ----------
Degese, M.S., Tanos, T., Naipauer, J., Gingerich, T., Chiappe, D., Echeverria, P., et al. "An interplay between the p38 MAPK pathway and AUBPs regulates c-fos mRNA stability during mitogenic stimulation" . Biochemical Journal, vol. 467, no. 1, 2015, pp. 77-90.
---------- VANCOUVER ----------
Degese, M.S., Tanos, T., Naipauer, J., Gingerich, T., Chiappe, D., Echeverria, P., et al. An interplay between the p38 MAPK pathway and AUBPs regulates c-fos mRNA stability during mitogenic stimulation. Biochem. J. 2015;467(1):77-90.