PIM2 regulates stemness through phosphorylation of 4E-BP1

Embryonic stem cells (ESCs) can undergo unlimited self-renewal and maintain pluripotency to differentiate into any cell type of the three germ layers. Extensive studies have shown ESC identity is regulated by transcription factors, epigenetic regulators and multiple signal transduction pathways. However, the kinase regulation of pluripotency is not well understood. Here we show that the serine/threonine kinase PIM2, which is highly expressed in ESCs but not in somatic cells, functions as a crucial stemness regulator in ESCs. Knockout of Pim2 inhibits the self-renewal and differentiation capability of ESCs. Mechanistic studies identified that PIM2 can directly phosphorylate 4E-BP1, leading to release of eIF4E which facilitates the translation of pluripotent genes in ESCs. Our study highlights a novel kinase cascade pathway for ESC identity maintenance.