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). 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 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. However, in Ba/F3-FT cells expression of the c-jun gene 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.
Shimizu
R
R
Department of Medicine, Jichi Medical School, Tochigi, Japan.
Komatsu
N
N
Nakamura
Y
Y
Nakauchi
H
H
Nakabeppu
Y
Y
Miura
Y
Y
D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D004921:Erythropoietin / Q000502:physiology*; D015870:Gene Expression; D016762:Genes, fos; D016758:Genes, jun; D006801:Humans; D051379:Mice; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D017467:Receptors, Erythropoietin / Q000502:physiology*; D015398:Signal Transduction
D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D017467:Receptors, Erythropoietin; D004921:Erythropoietin