PIM2 interacts with tristetraprolin and promotes breast cancer tumorigenesis

Tristetraprolin (TTP) is an AU‐rich element‐binding protein that regulates mRNA stability and plays important roles in cancer. The mechanisms by which TTP is regulated in breast cancer are poorly understood. Using multiple biochemical approaches, we found that proviral insertion in murine lymphomas 2 (PIM2) is a novel binding partner of TTP. Interestingly, PIM2 decreased TTP protein levels independent of its kinase activity. PIM2 instead targeted TTP protein for degradation via the ubiquitin‐proteasome pathway. Furthermore, immunohistochemical staining showed that PIM2 and TTP protein levels were negatively correlated in human breast cancer samples. Indeed, PIM2 overexpression de‐repressed TTP‐mediated inhibition of breast cancer cell proliferation and migration in vitro and promoted breast tumor xenograft growth in vivo. These findings demonstrate an important role for the PIM2‐TTP complex in breast cancer tumorigenesis, suggesting that PIM2 may represent a potential therapeutic target for breast cancer treatment. Tristetraprolin (TTP) is an AU‐rich element‐binding protein that regulates mRNA stability and is deregulated in some cancers. We have found that the oncogene Proviral Insertion in Murine Lymphomas 2 (PIM2) binds to TTP and decreases TTP protein levels by targeting it for degradation via the ubiquitin‐proteasome pathway. Furthermore, we report a key role for PIM2 in promoting breast cancer cell proliferation and tumour xenograft growth via its negative regulation of TTP.