P38? controls erythroblast enucleation and Rb signaling in stress erythropoiesis.

ABSTRACT: Enucleation of erythroblasts during terminal differentiation is unique to mammals. Although erythroid enucleation has been extensively studied, only a few genes, including retinoblastoma protein (Rb), have been identified to regulate nuclear extrusion. It remains largely undefined by which signaling molecules, the extrinsic stimuli, such as erythropoietin (Epo), are transduced to induce enucleation. Here, we show that p38?, a mitogen-activated protein kinase (MAPK), is required for erythroid enucleation. In an ex vivo differentiation system that contains high Epo levels and mimics stress erythropoiesis, p38? is activated during erythroid differentiation. Loss of p38? completely blocks enucleation of primary erythroblasts. Moreover, p38? regulates erythroblast enucleation in a cell-autonomous manner in vivo during fetal and anemic stress erythropoiesis. Markedly, loss of p38? leads to downregulation of p21, and decreased activation of the p21 target Rb, both of which are important regulators of erythroblast enucleation. This study demonstrates that p38? is a key signaling molecule for erythroblast enucleation during stress erythropoiesis.

SUBMITTER: Schultze SM 

PROVIDER: S-EPMC3292296 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature