CIP2A Constrains Th17 Differentiation by Modulating STAT3 Signaling
Mohd Moin Khan,
Ubaid Ullah,
Meraj H. Khan,
Lingjia Kong,
Robert Moulder,
Tommi Välikangas,
Santosh Dilip Bhosale,
Elina Komsi,
Omid Rasool,
Zhi Chen,
Laura L. Elo,
Jukka Westermarck,
Riitta Lahesmaa
Affiliations
Mohd Moin Khan
Turku Bioscience Centre, University of Turku and Åbo Akademi University, Tykistökatu 6A, Turku, Finland; Turku Doctoral Programme of Molecular Medicine (TuDMM), University of Turku, Turku, Finland
Ubaid Ullah
Turku Bioscience Centre, University of Turku and Åbo Akademi University, Tykistökatu 6A, Turku, Finland
Meraj H. Khan
Turku Bioscience Centre, University of Turku and Åbo Akademi University, Tykistökatu 6A, Turku, Finland
Lingjia Kong
Turku Bioscience Centre, University of Turku and Åbo Akademi University, Tykistökatu 6A, Turku, Finland; The Broad Institute of MIT and Harvard, Cambridge, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, USA
Robert Moulder
Turku Bioscience Centre, University of Turku and Åbo Akademi University, Tykistökatu 6A, Turku, Finland
Tommi Välikangas
Turku Bioscience Centre, University of Turku and Åbo Akademi University, Tykistökatu 6A, Turku, Finland; Doctoral Programme in Mathematics and Computer Sciences (MATTI), University of Turku, Turku, Finland
Santosh Dilip Bhosale
Turku Bioscience Centre, University of Turku and Åbo Akademi University, Tykistökatu 6A, Turku, Finland
Elina Komsi
Turku Bioscience Centre, University of Turku and Åbo Akademi University, Tykistökatu 6A, Turku, Finland
Omid Rasool
Turku Bioscience Centre, University of Turku and Åbo Akademi University, Tykistökatu 6A, Turku, Finland
Zhi Chen
Turku Bioscience Centre, University of Turku and Åbo Akademi University, Tykistökatu 6A, Turku, Finland; Faculty of Biochemistry and Molecular Medicine, University of Oulu
Laura L. Elo
Turku Bioscience Centre, University of Turku and Åbo Akademi University, Tykistökatu 6A, Turku, Finland
Jukka Westermarck
Turku Bioscience Centre, University of Turku and Åbo Akademi University, Tykistökatu 6A, Turku, Finland; Institute of Biomedicine, University of Turku, Turku, Finland
Riitta Lahesmaa
Turku Bioscience Centre, University of Turku and Åbo Akademi University, Tykistökatu 6A, Turku, Finland; Corresponding author
Summary: Cancerous 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. : Molecular Interaction; Immunology; Systems Biology; Omics Subject Areas: Molecular Interaction, Immunology, Systems Biology, Omics
