title: siRNA high-throughput kinase library screen identifies protein kinase, DNA-activated catalytic polypeptide to play a role in MyD88-induced IFNA2 activation and IL-8 secretion.
abstract: The discovery of RNA interference has led to the development of short interfering RNA (siRNA) screening, which has been widely used to study biological pathways. Here, we describe the development and validation of a system suitable to identify cellular genes involved in interferon A2 (IFNA2) promoter activation and interleukin (IL)-8 secretion downstream of MyD88. Forty genes were identified. Five genes were selected for further study. One gene, protein kinase, DNA-activated catalytic polypeptide (PRKDC), was confirmed to play a role in MyD88-induced IFNA2 activation and IL-8 secretion.
authors.affiliation: Biopharm Discovery, Medicines Research Centre, GlaxoSmithKline, Stevenage, Hertfordshire, UK. n.charlaftis@imperial.ac.uk
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Charlaftis
authors.forename: Douglas T
authors.initials: DT
authors.lastname: Fearon
authors.forename: Annett
authors.initials: A
authors.lastname: Schoenemeyer
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Morley
mesh_terms: D002470:Cell Survival; D051747:DNA-Activated Protein Kinase / Q000235:genetics / Q000378:metabolism*; D015723:Gene Library; D057809:HEK293 Cells; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics*; D016209:Interleukin-8 / Q000378:metabolism*; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: C554158:IFNA2 protein, human; D016898:Interferon-alpha; D016209:Interleukin-8; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human