PIM1 Protein, Human (Active)

The PIM1 protein, a proto-oncogene with serine/threonine kinase activity, plays a pivotal role in cell survival and proliferation, conferring a selective advantage in tumorigenesis. Its oncogenic activity involves the regulation of MYC transcriptional activity, cell cycle progression, and phosphorylation-mediated inhibition of proapoptotic proteins, including BAD, MAP3K5, and FOXO3. PIM1 phosphorylates MYC, enhancing its stability and transcriptional activity, potentially explaining the synergism between PIM1 and MYC in tumorigenesis. By phosphorylating BAD, PIM1 induces the release of the anti-apoptotic protein Bcl-X(L)/BCL2L1, promoting survival signaling. Additionally, PIM1 phosphorylates MAP3K5, inhibiting its kinase activity and suppressing MAP3K5-mediated apoptotic signaling. PIM1 stimulates cell cycle progression at G1-S and G2-M transitions by phosphorylating CDC25A and CDC25C, and it down-regulates the cell cycle regulator CDKN1B at both transcriptional and post-translational levels. PIM1 also impacts chromatin structure by phosphorylating HP1 gamma/CBX3 and acts as a regulator of homing and migration of bone marrow cells. Furthermore, PIM1 positively regulates mTORC1 signaling, inhibits drug sensitivity through ABCG2 phosphorylation and activation, and promotes brown adipocyte differentiation.