Functional Regulation of STAT3 by Phosphorylation and Acetylation Modifications

Abstract: STAT3 is a cytoplasmic transcriptional factor of cytokine and growth factor receptor. When cytokine binds Janus kinases (JAKs)-associated receptor， JAKs are activated by itself phosphorylation. Activated JAK can phosphorylate one or more receptor chains to generate docking sites for binding STAT3， and then STAT3 is phosphorylated on Tyr705 and Ser727 sites. Phosphorylated STAT3 dissociate from the receptor and form dimers， then translocate into the nucleus to regulate the gene expression. Recent studies indicated that Lys685 site of STAT3 can be modified by acetylation， which contributed to the formation of stable STAT3 dimers. In this study， to better understand the relationship between acetylation and phosphorylation modification of STAT3 and the important effect for regulation of STAT3 activity， we used Western blot and luciferase reporter assay etc to find that CBP can enhance the phosphorylation of Ser727 site and promote the transcriptional activation of STAT3. Moreover， the dephosphorylation of Tyr705 stie weakens to the level of STAT3 acetylation. The phosphorylation of Tyr705 site has a great influence on STAT3 transcriptional activation. The results provide a basis for cancer therapy through how to target the sustained activated STAT3.

CSTR: 32200.14.cjcb.2010.01.0018