Volume 22, No 3, Mar 2012

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 22 Issue 3, March 2012: 539-560

ORIGINAL ARTICLES

p38α controls erythroblast enucleation and Rb signaling in stress erythropoiesis

Simon M Schultze², Andreas Mairhofer¹, Dan Li², Jin Cen², Hartmut Beug^1,4, Erwin F Wagner² and Lijian Hui²

¹Research Institute of Molecular Pathology (IMP), Dr. Bohr-Gasse 7, A-1030, Vienna, Austria
²Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Yueyang Road 320, Shanghai 200031, China
³F-BBVA-CNIO Cancer Cell Biology Programme, Spanish National Cancer Research Centre, Melchor Fernández Almagro 3, E-28029, Madrid, Spain
⁴Deceased. While this manuscript was in revision, Dr Hartmut Beug passed away after a heroic fight against cancer. We dedicate this work to his memory. Correspondence: Lijian Hui,(ljhui@sibs.ac.cn)

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.

Cell Research (2012) 22:539-550. doi:10.1038/cr.2011.159; published online 27 September 2011

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