Role ofc-junin the Inhibition of Erythropoietin Receptor-Mediated Apoptosis

Abstract

Human bone marrow cells express both a truncated and full-length form of the erythropoietin receptor (EpoR-T and EpoR-F, respectively). Transfection experiments using the murine interleukin (IL)-3-dependent cell line, Ba/F3, revealed that the cells coexpressing EpoR-F and EpoR-T (Ba/F3-FT) were more likely to undergo programmed cell death (apoptosis) than cells expressing EpoR-F (Ba/F3-FF), even in the presence of erythropoietin (Epo). When Ba/F3-FF cells were stimulated with Epo or IL-3, rapid induction ofc-myc, c-fos, c-junandjunBgenes was observed. A similar effect was also seen in IL-3-stimulated Ba/F3-Ft cells. However, in Ba/F3-FT cells expression of thec-jungene was not induced by Epo stimulation. Administration of Epo could prevent apoptosis induced by IL-3 deprivation in Ba/F3-FT cells expressing ectopic c-Jun protein. These results indicate that induction of c-Jun through the Epo signaling pathway has an important role in the inhibition of apoptosis.