Attenuation of EPO-dependent erythroblast formation by death-associated protein kinase-2

作者：Fang Jing; Menon Madhu; Zhang Diya; Torbett Bruce; Oxburgh Leif; Tschan Mario; Houde Estelle; Wojchowski Don M^*

来源：Blood, 2008, 112(3): 886-890.

DOI：10.1182/blood-2008-02-138909

The adult erythron is maintained via dynamic modulation of erythroblast survival potentials. Toward identifying novel regulators of this process, murine splenic erythroblasts at 3 developmental stages were prepared, purified and profiled. Stage-to-stage modulated genes were then functionally categorized, with a focus on apoptotic factors. In parallel with BCL-X and NIX, death-associated protein kinase-2 (DAPK2) was substantially up-modulated during late erythropoiesis. Among hematopoietic lineages, DAPK2 was expressed predominantly in erythroid cells. In a Gata1-IE3.9int-DAPK2 transgenic mouse model, effects on steady-state reticulocyte and red blood cell (RBC) levels were limited. During hemolytic anemia, however, erythropoiesis was markedly deficient. Ex vivo analyses revealed heightened apoptosis due to DAPK2 at a Kit(-)CD71(high)Ter119(-) stage, together with a subsequent multifold defect in late-stage Kit(-)CD71(high)Ter119+ cell formation. In UT7epo cells, siRNA knockdown of DAPK2 enhanced survival due to cytokine withdrawal, and DAPK2's phosphorylation and kinase activity also were erythropoietin (EPO)-modulated. DAPK2 therefore comprises a new candidate attenuator of stress erythropoiesis.

• 出版日期2008-8-1
• 单位西北大学