B-myb transcriptional regulation and mRNA stability during differentiation of neuroblastoma cells.
B-myb and c-myb expression is high in neuroblastoma cells and declines during retinoic acid-induced differentiation. We show here that B-myb down-regulation during retinoic acid-induced differentiation of LAN-5 neuroblastoma cells occurs at the transcriptional level. In addition, we measured B-myb and c-myb messenger RNA half-lives, and found that, unlike c-myb, B-myb messenger RNA was remarkably stable (> 10 h). Inhibition of protein synthesis by treatment with cycloheximide increased B-myb messenger RNA levels, suggesting that one or more labile proteins act as repressors of B-myb transcription. In the same cell line, blocking protein synthesis decreased the level of c-myb mRNA under both normal and differentiative conditions. Thus, B-myb and c-myb undergo similar transcriptional regulation, but there are specific differences in the stability of their messenger RNAs and in the mechanisms through which their transcription is controlled. These differences could reflect different functional roles played by c-myb and B-myb in neuroblastoma cells.
Raschellà
G
G
Department of Biological and Environmental Sciences, Ente Nuove Technologie Energia e Ambiente CR Casaccia, Rome, Italy.
Negroni
A
A
Pucci
S
S
Amendola
R
R
Valeri
S
S
Calabretta
B
B
D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D003513:Cycloheximide / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D009447:Neuroblastoma; D010641:Phenotype; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D020598:Proto-Oncogene Proteins c-myb; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000201:enzymology
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C064352:MYBL2 protein, human; D011500:Protein Synthesis Inhibitors; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; D003513:Cycloheximide; D011505:Protein-Tyrosine Kinases