Ohbayashi Norihiko, Taira Naohisa, Kawakami Shiho, Togi Sumihito, Sato Noriko, Ikeda Osamu, Kamitani Shinya, Muromoto Ryuta, Sekine Yuichi, Matsuda Tadashi
Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Kita-ku Kita 12 Nishi 6, Sapporo 060-0812, Japan.
Biochem Biophys Res Commun. 2008 Aug 1;372(3):475-9. doi: 10.1016/j.bbrc.2008.05.073. Epub 2008 May 27.
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.
信号转导与转录激活因子3（STAT3）在许多生理过程中介导生物学作用，它通过特定的酪氨酸磷酸化、二聚化和核转位被细胞因子和生长因子激活。为了阐明STAT3激活调控的分子机制，我们进行了酵母双杂交筛选。我们鉴定出一种RNA结合蛋白Y14作为STAT3的新型结合伴侣。在体内，Y14通过STAT3的C末端区域与STAT3结合。重要的是，小干扰RNA介导的内源性Y14表达降低减少了IL-6诱导的STAT3酪氨酸磷酸化、核积累和DNA结合活性，以及IL-6/STAT3依赖的基因表达。这些结果表明，Y14与STAT3相互作用，并通过影响STAT3的酪氨酸磷酸化来调节STAT3的转录激活。
