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STAT3是细胞因子和生长因子受体的胞质转录因子。当细胞因子与JAK相连受体结合时,JAK通过自身磷酸化而被激活,激活后的JAK可磷酸化一个或多个受体位点并呈递给STAT3而与之结合。随后STAT3发生Tyr705和Ser727位点的磷酸化并从受体上解离,而后转移至细胞核中调控基因表达。近来有研究表明STAT3的Lys685可发生乙酰化修饰,并且它对STAT3二聚体的稳定形成非常重要。为了进一步研究STAT3的乙酰化与磷酸化修饰之间的关系以及对STAT3活性调节的影响,本文应用Western印迹和荧光素酶报告基因检测等方法发现CBP可以增强STAT3Ser727的磷酸化,增强STAT3的转录活性。此外,STAT3 Tyr705去磷酸化能减弱STAT3的乙酰化水平,而且Tyr705的磷酸化修饰对STAT3的转录活性影响很大。上述结果对于如何靶向持续激活的STAT3用于肿瘤治疗提供了依据。
STAT3 is a cytosolic and growth factor receptor cytosolic transcription factor. When a cytokine binds to a JAK-linked receptor, JAK is activated by autophosphorylation. Activated JAK phosphorylates one or more receptor sites and presents to STAT3 for binding. Subsequently, phosphorylation of Tyr705 and Ser727 sites occurs in STAT3 and dissociates from the receptor, which is then transferred to the nucleus to regulate gene expression. Recently, studies have shown that Lys685 of STAT3 can undergo acetylation modification, and it is very important for the stable formation of STAT3 dimer. In order to further study the relationship between STAT3 acetylation and phosphorylation modification and STAT3 activity regulation, we found that CBP can enhance the phosphorylation of STAT3Ser727 and enhance the transcriptional activity of STAT3 by Western blot and luciferase reporter assay . In addition, dephosphorylation of STAT3 Tyr705 attenuated the acetylation level of STAT3, and the phosphorylation of Tyr705 strongly influenced the transcriptional activity of STAT3. The above results provide a basis for how to target the sustained activation of STAT3 for tumor therapy.