PIM1: Human Proviral Integration Site for MulV
PDB Code: 1XWS
Pim1 is a cytoplasmic highly conserved serine/threonine kinase that was first discovered as a preferential proviral insertion site in Moloney Murine Leukemia Virus (MoMuLV) induced T-cell lymphomas. The expression pattern of Pim1 is widespread and the protein is over-expressed in a series of tumors but highest expression levels are found in cells of the hematopoietic and lymphoid system. Pim1 is induced by cytokines like interleukins and GM-CSF through the Jak/STAT pathway and has been therefore implemented in the proliferation and differentiation of blood cells. Pim1 has also been implicated directly in the regulation of the Jak/STAT pathway by stabilizing the negative regulator Socs-1. Furthermore, recent data indicates that Pim1 is linked to cell cycle control and apoptosis. We determined the structure of human Pim1 in complex with an inhibitor of the bisindolyl maleimide class. This inhibitor class has been developed for the inhibition of PKC kinase and a related compound is currently in phase III clinical trials as a potential drug against diabetes complications like diabetic retinopathy as well as ventricular hypertrophy in heart failure.
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