PIM = PROVIRUS INTEGRATION SITE FOR MOLONEY MURINE LEUKEMIA VIRUS KINASE
The PIM (Proviral Insertion site in Moloney murine leukemia virus) family includes the serine/threonine kinases PIM-1, PIM-2, and PIM-3.
The expression of PIM kinases is regulated largely through upstream JAK-STAT signaling.
PIM kinases bind to and stabilize the oncoprotein MYC, which plays a crucial role in cell cycle regulation.
PIM kinases phosphorylate a number of target molecules, several of which are common substrates with the PI3K/AKT pathway, including: • Activation of the mTORC1 complex, a key effector of the PI3K pathway that promotes cell survival. • Modifications of the ribosome-associated protein targets p70S6K and 4EBP, leading to increased protein synthesis. • Inhibition of the pro-apaptotic protein BAD, reducing cell death.
Dysregulated PIM activity may enhance cancer cell proliferation and survival in a variety of hematological malignancies and solid tumors.
Incyte is developing pan-inhibitors of PIM kinases.
PIM kinases are involved in cell cycle progression, survival, and transcriptional activation. The proteins are overexpressed in hematopoietic malignancies as well as in some solid tumors.
PIM expression is regulated by JAK/STAT, and PIM proteins have overlapping substrates with the PI3K/AKT pathway. Therefore, research in PIM inhibition is of interest in combination with inhibitors of JAK and PI3Kδ.