An RNA biding protein, Y14 interacts with and modulates STAT3 activation.
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.
Ohbayashi
Norihiko
N
Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Kita-ku Kita 12 Nishi 6, Sapporo 060-0812, Japan.
Taira
Naohisa
N
Kawakami
Shiho
S
Togi
Sumihito
S
Sato
Noriko
N
Ikeda
Osamu
O
Kamitani
Shinya
S
Muromoto
Ryuta
R
Sekine
Yuichi
Y
Matsuda
Tadashi
T
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
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