Work

The oncogene protein kinase PIM1 regulates mammalian erythroblast enucleation

Year: 2025

Type: article

Abstract: Erythroblast enucleation is a unique process during mammalian erythropoiesis, yet its regulatory mechanisms remain largely elusive. Here, we demonstrate the specific regulatory role of the oncogene PIM1, the most highly expressed protein kinase in orthochromatic erythroblasts, in enucleation. Unlike its well-established roles in cancer cell proliferation and survival, knockdown of PIM1 in human erythroid cells does not affect cell growth or apoptosis, but specifically inhibits erythroblast enucleation without altering differentiation. To elucidate the functional conservation of PIM1 in mammalian erythropoiesis, we generate Pim1 fl/fl EpoR Cre mice in which Pim1 is deleted in erythroid cells. Consistent with human erythropoiesis, deletion of Pim1 in mice has no detectable effect on apoptosis or differentiation of erythroid cells, but specifically inhibits erythroblast enucleation. Phosphoproteomic analysis reveals that PIM1 deficiency causes a pronounced decrease in phosphorylation of GTPase-associated proteins involved in actin assembly and vesicle trafficking. Functionally, this perturbation results in an aberrant distribution of F-actin and endocytic vesicles within enucleating cells. These findings reveal the unexpected role of PIM1 in normal erythropoiesis and enhance our understanding of mammalian erythroblast enucleation.

Source: Communications Biology

DOI: 10.1038/s42003-025-08869-0