p38α controls erythroblast enucleation and Rb signaling in stress erythropoiesis  

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

机构地区：[1]Research Institute of Molecular Pathology(IMP),Dr.Bohr-Gasse 7,A-1030,Vienna,Austria [2]Laboratory 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 [3]F-BB VA-CNIO Cancer Cell Biology Programme,Spanish National Cancer Research Centre,Melchor Fernandez Almagro 3,E-28029,Madrid,Spain

出　　处：《Cell Research》2012年第3期539-550,共12页细胞研究（英文版）

基　　金：Acknowledgments We are grateful to Dr U Klingmuller （German Cancer Research Center, Germany） for providing the ErGFPcre mice; Dr J Han （Univiersity of Xiamen, China） for providing the p38ct wild-type and AF mutant plasmids; V Komnenovic （IMP, Austria） for histological analyses; and G Litos and M Kerenyi for technical support. We thank L Bakiri for critical reading of the manuscript. The IMP is funded by Boehringer Ingelheim. Work in LH laboratory is funded by the National Natural Science Foundation of China （30623003, 31071238）, Shanghai Pujiang Program （09P J1411200） and the Knowledge Innovation Program of Shanghai Institutes for Biological Sciences （2009KIP101）. Work in EFW laboratory is supported by a grant from F-BBVA and an ERC-Advanced grant ERC-FCK/2008/37.

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 thatp38α, 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, p38αis 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 kev signaling molecule for ervthroblast enucleation during stress ervthronaiesis.

关 键 词：p38α ENUCLEATION stress erythropoiesis Rb p38α ENUCLEATION stress erythropoiesis RB 

分 类 号：Q26[生物学—细胞生物学] TQ464.7[化学工程—制药化工]