title: p38α 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 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 molecule for erythroblast enucleation during stress erythropoiesis.
authors.affiliation: Research Institute of Molecular Pathology (IMP), Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.
authors.forename: Simon M
authors.initials: SM
authors.lastname: Schultze
authors.forename: Andreas
authors.initials: A
authors.lastname: Mairhofer
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Jin
authors.initials: J
authors.lastname: Cen
authors.forename: Hartmut
authors.initials: H
authors.lastname: Beug
authors.forename: Erwin F
authors.initials: EF
authors.lastname: Wagner
authors.forename: Lijian
authors.initials: L
authors.lastname: Hui
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004900:Erythroblasts / Q000166:cytology / Q000378:metabolism*; D004920:Erythropoiesis; D051379:Mice; D048308:Mitogen-Activated Protein Kinase 14 / Q000172:deficiency / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D016160:Retinoblastoma Protein; D048308:Mitogen-Activated Protein Kinase 14