title: ERK8 is a novel HuR kinase that regulates tumour suppressor PDCD4 through a miR-21 dependent mechanism.
abstract: Programmed cell death 4 (PDCD4) is a tumour suppressor implicated in cancer development and progression and was recently identified as a repressor of cap-independent translation of specific genes involved in the regulation of apoptosis. We show that the RNA-binding protein HuR binds to the PDCD4 3'UTR to protect it from miR-21-induced silencing. However, following H2O2 treatment, PDCD4 mRNA is degraded via miR-21 binding. Importantly, we identify HuR as a novel substrate of the ERK8 kinase pathway in response to H2O2 treatment. We show that phosphorylation of HuR by ERK8 prevents it from binding to PDCD4 mRNA and allows miR-21-mediated degradation of PDCD4.
authors.affiliation: Molecular Biomedicine Program, Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada.
authors.forename: Urszula
authors.initials: U
authors.lastname: Liwak-Muir
authors.affiliation: Molecular Biomedicine Program, Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada.
authors.forename: Christine C
authors.initials: CC
authors.lastname: Dobson
authors.affiliation: Molecular Biomedicine Program, Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada.
authors.forename: Thet
authors.initials: T
authors.lastname: Naing
authors.affiliation: Molecular Biomedicine Program, Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada.
authors.forename: Quinlan
authors.initials: Q
authors.lastname: Wylie
authors.affiliation: Molecular Biomedicine Program, Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada.
authors.forename: Lucia
authors.initials: L
authors.lastname: Chehade
authors.affiliation: Molecular Biomedicine Program, Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Baird
authors.affiliation: Department of Pediatrics, University of Ottawa, Ottawa, ON, Canada.|Newborn Screening Ontario, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Pranesh K
authors.initials: PK
authors.lastname: Chakraborty
authors.affiliation: Molecular Biomedicine Program, Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada.|Department of Pediatrics, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Holcik
mesh_terms: D020413:3' Untranslated Regions; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D000067780:ELAV-Like Protein 1 / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D034622:RNA Interference; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D002583:Uterine Cervical Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology
chemical_list: D020413:3' Untranslated Regions; D051017:Apoptosis Regulatory Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C114487:PDCD4 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D006861:Hydrogen Peroxide; D048049:Extracellular Signal-Regulated MAP Kinases; C456320:MAPK15 protein, human
keywords: kinase; miRNA; tumour supressor