ROLE OF C-JUN IN THE INHIBITION OF ERYTHROPOIETIN RECEPTOR-MEDIATED APOPTOSIS

Human bone marrow cells express both a truncated and full-length form of the erythropoietin receptor (EpoR-T and EpoR-F, respectively). Tran sfection experiments using the murine interleukin (IL)-3-dependent cel l Line, Ba/F3, revealed that the cells coexpressing EpoR-F and EpoR-T (Ba/F3-FT) were more likely to undergo programmed cell death (apoptosi s) than cells expressing EpoR-F (Ba/F3-FF), even in the presence of er ythropoietin (Epo). When Ba/F3-FF cells were stimulated with Epo or IL -3, rapid induction of c-myc, c-fos, c-jun and junB genes was observed . A similar effect was also seen in IL-3-stimulated Ba/F3-Ft cells. Ho wever, in Ba/F3-FT cells expression of the c-jun gene was not induced by Epo stimulation. Administration of Epo could prevent apoptosis indu ced by IL-3 deprivation in Ba/F3-FT cells expressing ectopic c-Jun pro tein. These results indicate that induction of c-Jun through the Epo s ignaling pathway has an important role in the inhibition of apoptosis. (C) 1996 Academic Press. Inc.