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http://purl.uniprot.org/citations/25124043http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/25124043http://www.w3.org/2000/01/rdf-schema#comment"The basic helix-loop-helix transcription factor hASH1, encoded by the ASCL1 gene, plays an important role in neurogenesis and tumor development. Recent findings indicate that local oxygen tension is a critical determinant for the progression of neuroblastomas. Here we investigated the molecular mechanisms underlying the oxygen-dependent expression of hASH1 in neuroblastoma cells. Exposure of human neuroblastoma-derived Kelly cells to 1% O2 significantly decreased ASCL1 mRNA and hASH1 protein levels. Using reporter gene assays, we show that the response of hASH1 to hypoxia is mediated mainly by post-transcriptional inhibition via the ASCL1 mRNA 5'- and 3'-UTRs, whereas additional inhibition of the ASCL1 promoter was observed under prolonged hypoxia. By RNA pulldown experiments followed by MALDI/TOF-MS analysis, we identified heterogeneous nuclear ribonucleoprotein (hnRNP)-A2/B1 and hnRNP-R as interactors binding directly to the ASCL1 mRNA 5'- and 3'-UTRs and influencing its expression. We further demonstrate that hnRNP-A2/B1 is a key positive regulator of ASCL1, findings that were also confirmed by analysis of a large compilation of gene expression data. Our data suggest that a prominent down-regulation of hnRNP-A2/B1 during hypoxia is associated with the post-transcriptional suppression of hASH1 synthesis. This novel post-transcriptional mechanism for regulating hASH1 levels will have important implications in neural cell fate development and disease."xsd:string
http://purl.uniprot.org/citations/25124043http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m114.579391"xsd:string
http://purl.uniprot.org/citations/25124043http://purl.uniprot.org/core/author"Scholz H."xsd:string
http://purl.uniprot.org/citations/25124043http://purl.uniprot.org/core/author"Benko E."xsd:string
http://purl.uniprot.org/citations/25124043http://purl.uniprot.org/core/author"Meier J.C."xsd:string
http://purl.uniprot.org/citations/25124043http://purl.uniprot.org/core/author"Mrowka R."xsd:string
http://purl.uniprot.org/citations/25124043http://purl.uniprot.org/core/author"Persson P.B."xsd:string
http://purl.uniprot.org/citations/25124043http://purl.uniprot.org/core/author"Kasim M."xsd:string
http://purl.uniprot.org/citations/25124043http://purl.uniprot.org/core/author"Fahling M."xsd:string
http://purl.uniprot.org/citations/25124043http://purl.uniprot.org/core/author"Winkelmann A."xsd:string
http://purl.uniprot.org/citations/25124043http://purl.uniprot.org/core/author"Staudacher J.J."xsd:string
http://purl.uniprot.org/citations/25124043http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/25124043http://purl.uniprot.org/core/name"J Biol Chem"xsd:string
http://purl.uniprot.org/citations/25124043http://purl.uniprot.org/core/pages"26973-26988"xsd:string
http://purl.uniprot.org/citations/25124043http://purl.uniprot.org/core/title"Shutdown of achaete-scute homolog-1 expression by heterogeneous nuclear ribonucleoprotein (hnRNP)-A2/B1 in hypoxia."xsd:string
http://purl.uniprot.org/citations/25124043http://purl.uniprot.org/core/volume"289"xsd:string
http://purl.uniprot.org/citations/25124043http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/25124043
http://purl.uniprot.org/citations/25124043http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/25124043
http://purl.uniprot.org/uniprot/#_A0A024RA28-mappedCitation-25124043http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25124043
http://purl.uniprot.org/uniprot/#_A6IFL1-mappedCitation-25124043http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25124043
http://purl.uniprot.org/uniprot/#_A0A384NL58-mappedCitation-25124043http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25124043
http://purl.uniprot.org/uniprot/#_A0A7I2V4N1-mappedCitation-25124043http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25124043
http://purl.uniprot.org/uniprot/#_A7VJC2-mappedCitation-25124043http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25124043
http://purl.uniprot.org/uniprot/#_B2GV69-mappedCitation-25124043http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25124043