Khan, M. M., Ullah, U., Khan, M. H., Kong, L., Moulder, R., Välikangas, T., Bhosale, S. D., Komsi, E., Rasool, O., Chen, Z., Elo, L. L., Westermarck, J., & Lahesmaa, R. (2020). CIP2A Constrains Th17 Differentiation by Modulating STAT3 Signaling. iScience, 23(3), 100947. https://doi.org/10.1016/j.isci.2020.100947
CIP2A constrains Th17 differentiation by modulating STAT3 signaling
|Author:||Khan, Mohd Moin1,2; Ullah, Ubaid1; Khan, Meraj H.1;|
1Turku Bioscience Centre, University of Turku and Åbo Akademi University, Tykistökatu 6A, Turku, Finland
2Turku Doctoral Programme of Molecular Medicine (TuDMM), University of Turku, Turku, Finland
3The Broad Institute of MIT and Harvard, Cambridge, USA
4Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, USA
5Doctoral Programme in Mathematics and Computer Sciences (MATTI), University of Turku, Turku, Finland
6Faculty of Biochemistry and Molecular Medicine, University of Oulu
7Institute of Biomedicine, University of Turku, Turku, Finland
|Online Access:||PDF Full Text (PDF, 32 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2020042219672
|Publish Date:|| 2020-04-22
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.
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
M.M.K. was supported by University of Turku graduate school on Turku Doctoral Programme of Molecular Medicine (TuDMM) as well as a central grant from Finnish Cultural Foundation. R.L. was supported by the Academy of Finland, AoF, Centre of Excellence in Molecular Systems Immunology and Physiology Research (2012-2017) grant 250114; by the AoF grants 292335, 294337, 292482, and 31444; by grants from the JDRF; the Sigrid Jusélius Foundation; and the Finnish Cancer Foundation. Z.C. was funded by Academy of Finland grant no. 258313, and J.W. was funded by Sigrid Jusélius Foundation.
© 2020 The Authors. This is an open access article under the CC BY-NC-ND license http://creativecommons.org/licenses/by-nc-nd/4.0/).