p38α controls erythroblast enucleation and Rb signaling in stress erythropoiesis

p38α controls erythroblast enucleation and Rb

signaling in stress erythropoiesis

Simon M Schultze;Andreas Mairhofer;Dan Li;Jin Cen;Hartmut Beug;Erwin F Wagner;Lijian Hui

【期刊名称】《细胞研究（英文版）》 【年(卷),期】2012(022)003

【摘要】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 p38α,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,p38α is activated during erythroid differentiation.Loss of p38α completely blocks enucleation of primary erythroblasts.Moreover,p38α regulates erythroblast enucleation in a cell-autonomous manner in vivo during fetal and anemic stress erythropoiesis.Markedly,loss of p38α 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 p38α is a key signaling