title: A New STAT3-binding Partner, ARL3, Enhances the Phosphorylation and Nuclear Accumulation of STAT3.
abstract: Signal transducer and activator of transcription 3 (STAT3) is involved in cell proliferation, differentiation, and cell survival during immune responses, hematopoiesis, neurogenesis, and other biological processes. STAT3 activity is regulated by a variety of mechanisms, including phosphorylation and nuclear translocation. To clarify the molecular mechanisms underlying the regulation of STAT3 activity, we performed yeast two-hybrid screening. We identified ARL3 (ADP-ribosylation factor-like 3) as a novel STAT3-binding partner. ARL3 recognizes the DNA-binding domain as well as the C-terminal region of STAT3 in vivo, and their binding was the strongest when both proteins were activated. Importantly, small interfering RNA-mediated reduction of endogenous ARL3 expression decreased IL-6-induced tyrosine phosphorylation, nuclear accumulation, and transcriptional activity of STAT3. These results indicate that ARL3 interacts with STAT3 and regulates the transcriptional activation of STAT3 by influencing its nuclear accumulation of STAT3.
authors.affiliation: From the Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12 Nishi-6, Kita-Ku, Sapporo, 060-0812 and.
authors.forename: Sumihito
authors.initials: S
authors.lastname: Togi
authors.affiliation: From the Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12 Nishi-6, Kita-Ku, Sapporo, 060-0812 and.
authors.forename: Ryuta
authors.initials: R
authors.lastname: Muromoto
authors.affiliation: From the Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12 Nishi-6, Kita-Ku, Sapporo, 060-0812 and.
authors.forename: Koki
authors.initials: K
authors.lastname: Hirashima
authors.affiliation: From the Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12 Nishi-6, Kita-Ku, Sapporo, 060-0812 and.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kitai
authors.affiliation: From the Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12 Nishi-6, Kita-Ku, Sapporo, 060-0812 and.
authors.forename: Taichiro
authors.initials: T
authors.lastname: Okayama
authors.affiliation: From the Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12 Nishi-6, Kita-Ku, Sapporo, 060-0812 and.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ikeda
authors.affiliation: From the Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12 Nishi-6, Kita-Ku, Sapporo, 060-0812 and.
authors.forename: Naoki
authors.initials: N
authors.lastname: Matsumoto
authors.affiliation: From the Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12 Nishi-6, Kita-Ku, Sapporo, 060-0812 and.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kon
authors.affiliation: From the Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12 Nishi-6, Kita-Ku, Sapporo, 060-0812 and.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sekine
authors.affiliation: the Department of Hematology and Oncology, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Oritani
authors.affiliation: From the Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12 Nishi-6, Kita-Ku, Sapporo, 060-0812 and tmatsuda@pharm.hokudai.ac.jp.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsuda
mesh_terms: D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism*; D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000235:genetics; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D020727:ADP-Ribosylation Factors; C490247:ARL3 protein, human
keywords: STAT3; gene transcription; nuclear translocation; protein phosphorylation; signal transduction