p-Y705, S727 STAT3 dimer binds ICOS promoter

STAT3 binds to a region of the ICOS promoter downstream of NPM-ALK as assessed by electrophoretic mobility shift assay and chromatin immunoprecipitation. Although the phosphorylation status of STAT3 was not directly examined in the context of the ICOS promoter, STAT3 is a known NPM-ALK target and the stimulation of ICOS expression is dependent on NPM-ALK kinase activity (Zhang et al, 2011; reviewed in Chiarle et al, 2008; Ducray et al, 2019). STAT3 also contributes to ICOS expression through the downregulation of miR-219, a negative regulator of ICOS (Zhang et al, 2011).

STAT3通过电泳迁移率变动实验和染色质免疫沉淀实验被确认为与ICOS启动子下游的NPM-ALK结合区域相互作用。尽管在ICOS启动子的背景下并未直接检测STAT3的磷酸化状态，但STAT3已知是NPM-ALK的靶标，且ICOS表达刺激依赖于NPM-ALK激酶活性（Zhang等，2011；参见Chiarle等，2008年的综述；Ducray等，2019年）。此外，STAT3通过下调ICOS的负调控因子miR-219，亦参与ICOS表达的调控（Zhang等，2011）。