LIF- and IL-6-Induced Acetylation of STAT3 at Lys-685 through PI3K/Akt 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 or serine phosphorylation, dimerization and nuclear translocation. A recent study has demonstrated, by using antibody to acetylated lysine, and a STAT3 mutant with Lys-685-to-Arg substitution, that STAT3 is acetylated at Lys-685 by histone acetyltransferase p300, and that acetylation at Lys-685 is critical for STAT3 activation. In the present study, we created an acetyl-specific antibody against STAT3 acetylated at Lys-685, and found that leukemia inhibitory factor (LIF) or interleukin (IL)-6 induced acetylation of STAT3 at Lys-685 in 293T and Hep3B cells. Moreover, acetylation of STAT3 at Lys-685 was suppressed by PI3K inhibitor LY294002, or a dominant negative Akt. Taken together, our findings demonstrate that endogenous STAT3 is acetylated at Lys-685 by LIF or IL-6 through PI3K/Akt activation

Interactions between STAT3 and Y14

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

Interactions between STAT3 and Y14

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

Interactions between Y14, MAGOH and STAT3

Signal transducer and activator of transcription 3 (STAT3), which is activated by cytokines and growth factors, mediates biological actions in many physiological processes. In a previous study, we found that Y14, a core component of the exon-junction complex (EJC) bound to STAT3 and upregulated the transcriptional activity of STAT3 by influencing its DNA-binding activity. In the present study, we demonstrate that STAT3 endogenously interacts with Y14. In addition, we found that MAGOH, a Y14 partner in the EJC, inhibits the STAT3-Y14 complex formation. Furthermore, small-interfering RNA-mediated reduction of MAGOH expression enhanced interleukin-6-induced gene expression. These results indicate that MAGOH regulates the transcriptional activation of STAT3 by interfering complex formation between STAT3 and Y14