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.

journal_name

Cell Res

journal_title

Cell research

authors

Schultze SM,Mairhofer A,Li D,Cen J,Beug H,Wagner EF,Hui L

doi

10.1038/cr.2011.159

subject

Has Abstract

pub_date

2012-03-01 00:00:00

pages

539-50

issue

3

eissn

1001-0602

issn

1748-7838

pii

cr2011159

journal_volume

22

pub_type

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