摘要：SummaryCancerous Inhibitor of Protein Phosphatase 2A (CIP2A) is an oncogene and a potential cancer therapy target protein. Accordingly, a better understanding of the physiological function of CIP2A, especially in the context of immune cells, is a prerequisite for its exploitation in cancer therapy. Here, we report that CIP2A negatively regulates interleukin (IL)-17 production by Th17 cells in human and mouse. Interestingly, concomitant with increased IL-17 production, CIP2A-deficient Th17 cells had increased strength and duration of STAT3 phosphorylation. We analyzed the interactome of phosphorylated STAT3 in CIP2A-deficient and CIP2A-sufficient Th17 cells and indicated together with genome-wide gene expression profiling, a role of Acylglycerol Kinase (AGK) in the regulation of Th17 differentiation by CIP2A. We demonstrated that CIP2A regulates the strength of the interaction between AGK and STAT3, and thereby modulates STAT3 phosphorylation and expression of IL-17 in Th17 cells.Graphical AbstractDisplay OmittedHighlights•CIP2A deficiency leads to increased IL-17 production by Th17 cells•STAT3 phosphorylation is increased and prolonged in CIP2A-deficient Th17 cells•Mass spectrometry-based analysis of pSTAT3 interactome•CIP2A regulates interaction between acylglycerol kinase (AGK) and pSTAT3Molecular Interaction; Immunology; Systems Biology; Omics
