| First Author | Fang J | Year | 2008 |
| Journal | Blood | Volume | 112 |
| Issue | 3 | Pages | 886-90 |
| PubMed ID | 18535204 | Mgi Jnum | J:138409 |
| Mgi Id | MGI:3805131 | Doi | 10.1182/blood-2008-02-138909 |
| Citation | Fang J, et al. (2008) Attenuation of EPO-dependent erythroblast formation by death-associated protein kinase-2. Blood 112(3):886-90 |
| abstractText | 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 ana-lyses 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 knock-down 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. |
