Ruolo della chinasi PIM1 in risposta allo stress ribosomale

PIM1 is an oncogenic serine/threonine kinase mainly expressed in hematopoietic cells. Expression of PIM1 is regulated by a variety of growth factors and cytokines from transcriptional to post-translational level. Together with the other two members of the family (PIM2 and PIM3), PIM1 plays a role in hematopoietic cell growth and survival. By studying the molecular mechanisms of Diamond-Blackfan Anemia (DBA) we have found out that PIM1 interacts with the ribosomal protein RPS19 and cosediments with ribosomes. RPS19 gene is mutated in roughly one fourth of DBA patients, causing a defect in hematopoiesis due to an excess of apoptosis of erythroid precursors. To investigate the possible implication of PIM1 in DBA pathogenesis we have here analyzed the expression of this kinase in cultured cell model systems. These include a stably transfected cell line, inducible for PIM1 overexpression (PIM-REx) and an hematopoietic cell line (K562C), inducible for RPS19 downregulation. We have found that the depletion of RPS19 causes a drastic destabilization of PIM1 partly dependent on proteasome. The rapid degradation of PIM1 could be responsible for some defects observed in cells from DBA patients.