CIP2A Constrains Th17 Differentiation by Modulating STAT3 Signaling
Riitta Lahesmaa; Tommi Välikangas; Omid Rasool; Zhi Chen; Mohd Moin Khan; Lingjia Kong; Meraj H. Khan; Robert Moulder; Santosh Dilip Bhosale; Laura L. Elo; Jukka Westermarck; Ubaid Ullah; Elina Komsi
CIP2A Constrains Th17 Differentiation by Modulating STAT3 Signaling
Riitta Lahesmaa
Tommi Välikangas
Omid Rasool
Zhi Chen
Mohd Moin Khan
Lingjia Kong
Meraj H. Khan
Robert Moulder
Santosh Dilip Bhosale
Laura L. Elo
Jukka Westermarck
Ubaid Ullah
Elina Komsi
Cell Press, Elsevier Inc.
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042825917
https://urn.fi/URN:NBN:fi-fe2021042825917
Tiivistelmä
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.
Kokoelmat
- Rinnakkaistallenteet [19207]