The Novel Function and Molecular Mechanism of an Adapter Protein in Erythroid Differentiation

Erythroid cells play an important role to supply oxygen toward various tissues and organs and are generated through the process of erythropoiesis. In addition to erythropoietin (EPO), putative new positive and negative regulators have been proposed to act coordinately to control red cell production under normal and anemic conditions. Hence, unveiling new molecules that regulate the survival and maturation of erythroblasts are clinically important and relevant to the anemia of chemotherapy and chronic diseases such as myelodysplasia and multiple myeloma. Recently, we demonstrated that Disabled-2 (DAB2) is up-regulated during sodium butyrate-mediated erythroid differentiation of K562 chronic myeloid leukemic cells. Using DAB2-deficient K562 subline and siDAB2-expressing, DAB2-knockdown stable line, we further showed that DAB2 is a positive regulator in erythroid differentiation that represents the first report that links DAB2 function with erythroid differentiation. However, the detailed mechanisms and functions for DAB2 in erythroid differentiation are largely unknown. The cellular factors that are involved in the regulation of DAB2 expression are also not clear. In this three years grant proposal, we plan to unveil the functions and regulation of DAB2 during erythroid differentiation. At the first year, we will establish ex vivo and murine embryonic stem cell erythroid differentiation system for analysis of DAB2 expression and its implication in erythroid differentiation. At the second and third year, we will determine the molecular mechanisms that control DAB2 expression during erythroid differentiation. In addition, we will characterize DAB2-meidated cellular signaling and determine its importance in the regulation of erythroid differentiation. Together, the accomplishment of this grant proposal will clarify the functional role of DAB2 in erythropoiesis.

Project ID:PC9709-0933
External Project ID:NSC97-2320-B182-009-MY3