Prolonged expression of c-jun and associated activity of the transcription factor AP-1, during apoptosis in a human leukaemic cell line.
The product of the c-jun gene is a component of the transcription factor AP-1, which plays a critical regulatory role in the cellular response to certain proliferative stimuli. In this report, we demonstrate the prolonged expression of c-jun mRNA during apoptosis induced in a human leukaemic T-cell line, CEM C7, by treatment with either dexamethasone or gamma-radiation. However, overexpression of the c-jun mRNA was not accompanied by either increased expression of jun protein, or increased AP-1 DNA binding activity. Indeed, a decrease in AP-1 DNA binding activity was seen in response to both inducing stimuli. This decrease in AP-1 binding activity may be mediated by an increase in the activity of an AP-1 inhibitory factor, as the steady state levels of jun protein remained constant during the onset of apoptosis, and cytosolic AP-1 inhibitory activity was found to increase, concomitant with the decrease in AP-1 DNA binding activity. Our data demonstrate the complexity of the mechanisms involved in the regulation of c-jun expression during the onset of apoptosis, and suggest a novel mode for the regulation of AP-1 activity during the cessation of proliferation.
Goldstone
S D
SD
Department of Pathology, University of Sydney, NSW, Australia.
Lavin
M F
MF
D017209:Apoptosis; D004247:DNA / Q000378:metabolism; D015973:Gene Expression Regulation, Leukemic; D016758:Genes, jun; D006801:Humans; D015458:Leukemia, T-Cell / Q000235:genetics* / Q000473:pathology; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured
D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D004247:DNA