The delayed induction of c-jun in apoptotic human leukemic lymphoblasts is primarily transcriptional.
Because of their ability to induce lymphoid cell apoptosis, glucocorticoids have been used for decades to treat certain human leukemias and lymphomas. Studies presented in this paper complement our previous work demonstrating that sustained induction of the proto-oncogene c-jun plays a crucial role in the glucocorticoid-induced apoptotic pathway in CEM cells, human leukemic lymphoblasts. Results from measurements of c-jun mRNA half-life with RNase protection assays and of transcription by nuclear run-on assays indicate that, in the dexamethasone-sensitive cloned CEM-C7 cells, c-jun is induced at the transcriptional level. Consideration of time-course, however, suggested that this might be a secondary or possibly a delayed primary response. Use of cycloheximide to block protein synthesis strongly induced c-jun mRNA, suggesting that there had been relief from a labile protein repressor of transcription. Comparing the level of induction by cycloheximide with that of dexamethasone indicated that the two did not induce by an identical mechanism. The high induction by cycloheximide obscured simple interpretation of elevated c-jun mRNA levels after concomitant administration of cycloheximide and dexamethasone. This was resolved by nuclear run-on experiments, which showed that the dexamethasone induction of c-jun mRNA in this system does require protein synthesis.
Zhou
F
F
Department of Human Biological Chemistry and Genetics, The University of Texas Medical Branch, Galveston, TX 77555-0645, USA.
Medh
R D
RD
Zhang
W
W
Ansari
N H
NH
Thompson
E B
EB
D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D002458:Cell Fractionation; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004789:Enzyme Activation; D005260:Female; D005786:Gene Expression Regulation; D016758:Genes, jun; D005938:Glucocorticoids / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007945:Leukemia, Lymphoid; D008214:Lymphocytes / Q000502:physiology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D005938:Glucocorticoids; C000715470:MAS1 protein, human; D011500:Protein Synthesis Inhibitors; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D003513:Cycloheximide; D020169:Caspases