Pim2-flox Mouse

Pim2, also known as proviral integration site for Moloney murine leukemia virus 2, is a serine/threonine protein kinase functioning as an oncogene. It promotes transcriptional activation of genes involved in cell survival, proliferation, and cell-cycle progression. Pim2 is associated with multiple signaling pathways, such as p38 MAPK/Erk, NF-κB, and the TAK1-PIM2 pathway, and plays a significant role in various biological processes and diseases [2,4].

In hepatocellular carcinoma, PIM2 expression induced by pro-inflammatory macrophages suppresses immunotherapy efficacy. Mechanistically, IL1β from IFNγ-polarized tumor macrophages triggers PIM2 expression in cancer cells via p38 MAPK/Erk and NF-κB signaling pathways, endowing cancer cells with aggressive features [1].

In ovarian endometriosis, PIM2 promotes disease development by enhancing glycolysis and fibrosis. The PIM2 inhibitor SMI-4a can inhibit endometriosis development, and a PIM2 knockout mouse model demonstrated PIM2's role in vivo [3].

In multiple myeloma, up-regulation of the TAK1-PIM2 pathway in bone marrow stromal cells, osteoclasts, and MM cells in bone lesions plays a critical role in tumor expansion and bone destruction [4].

In solid tumors, PIM2 promotes cancer progression. The pan-PIM inhibitor JP11646 induces apoptosis, at least partly through PIM2 protein degradation, and suppresses cancer cell proliferation in vitro and in vivo [5].

In endometriosis, PIM2 phosphorylates PFKFB4, promoting anaerobic glycolysis and cell proliferation [6].

In acute lung injury induced by sepsis, knockdown of PIM2 alleviated LPS-induced bronchial epithelial cell injury by inhibiting the TLR2/MyD88 pathway [7].

In breast cancer, PIM2 phosphorylates USP27X, promoting glycolysis and breast cancer progression via deubiquitylation of MYC, which was also validated in PIM2-knockout mice [8].

In inflammatory arthritis, conditional knockout of Pim2 in macrophages or administration of the Pim2 inhibitor HJ-PI01 attenuated arthritis development by inhibiting M1 macrophage polarization [9].

In B-cell differentiation, PIM2 promotes cell cycle progression during the final stage of differentiation and inhibits Caspase 3 activation [10].

In conclusion, Pim2 has diverse functions in cell survival, proliferation, and metabolism-related processes. Pim2 knockout or conditional knockout mouse models have revealed its significance in various disease areas, including cancer, endometriosis, inflammatory arthritis, and acute lung injury, providing potential therapeutic targets for these diseases.