title: An RNA biding protein, Y14 interacts with and modulates STAT3 activation.
abstract: Signal transducer and activator of transcription 3 (STAT3), which mediates biological actions in many physiological processes, is activated by cytokines and growth factors via specific tyrosine-phosphorylation, dimerization, and nuclear translocation. To clarify the molecular mechanisms underlying the regulation of STAT3 activation, we performed yeast two-hybrid screening. We identified Y14, an RNA-binding protein, as a novel STAT3 binding partner. Y14 bound to STAT3 through the C-terminal region of STAT3 in vivo. Importantly, small-interfering RNA-mediated reduction of endogenous Y14 expression decreased IL-6-induced tyrosine-phosphorylation, nuclear accumulation, and DNA-binding activity of STAT3, as well as IL-6/STAT3-dependent gene expression. These results indicate that Y14 interacts with STAT3 and regulates the transcriptional activation of STAT3 by influencing the tyrosine-phosphorylation of STAT3.
authors.affiliation: Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Kita-ku Kita 12 Nishi 6, Sapporo 060-0812, Japan.
authors.forename: Norihiko
authors.initials: N
authors.lastname: Ohbayashi
authors.forename: Naohisa
authors.initials: N
authors.lastname: Taira
authors.forename: Shiho
authors.initials: S
authors.lastname: Kawakami
authors.forename: Sumihito
authors.initials: S
authors.lastname: Togi
authors.forename: Noriko
authors.initials: N
authors.lastname: Sato
authors.forename: Osamu
authors.initials: O
authors.lastname: Ikeda
authors.forename: Shinya
authors.initials: S
authors.lastname: Kamitani
authors.forename: Ryuta
authors.initials: R
authors.lastname: Muromoto
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sekine
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsuda
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques; D014443:Tyrosine / Q000378:metabolism
chemical_list: D015850:Interleukin-6; C406243:RBM8A protein, human; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014443:Tyrosine; D004247:DNA