cAMP-induced NF-κB (p50/relB) binding to a c-myb intronic enhancer correlates with c-myb up-regulation and inhibition of erythroleukemia cell differentiation
| Autor: | Modem Suhasini, E P Reddy, C D Reddy, Renate B. Pilz, J A DiDonato |
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| Rok vydání: | 1997 |
| Předmět: |
Cancer Research
JUNB Cellular differentiation Biology Mice chemistry.chemical_compound Genes Reporter hemic and lymphatic diseases Gene expression Cyclic AMP Tumor Cells Cultured Genetics Animals MYB RNA Messenger Enhancer Molecular Biology Transcription factor Forskolin RELB Colforsin NF-kappa B Cell Differentiation Oncogenes Introns Cell biology Enhancer Elements Genetic chemistry Cancer research Leukemia Erythroblastic Acute Protein Binding Subcellular Fractions Transcription Factors |
| Zdroj: | Oncogene. 15:1859-1870 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/sj.onc.1201530 |
| Popis: | During hexamethylene bisactamide (HMBA)-induced differentiation of murine erythroleukemia (MEL) cells erythroid genes are transcriptionally activated while c-myb and several other nuclear proto-oncogenes are down-regulated. Differentiation is inhibited by cAMP analogues and the adenyl cyclase-stimulating agent forskolin. We found that these drugs prevented the late down-regulation of c-myb which is known to be critical for MEL cell differentiation. Since the increase in c-myb mRNA levels was due to increased mRNA transcription, we examined the transcription factors NF-kappaB and AP-1 which have been implicated in the regulation of c-myb expression. Binding of MEL cell nuclear proteins to a NF-kappaB recognition sequence in c-myb intron I was strongly induced by 8-Br-cAMP or forskolin; induction was delayed and correlated with the up-regulation of c-myb. The cAMP-induced NF-kappaB complex contained p50 and RelB; in co-transfection assays, p50 and RelB transactivated a reporter construct containing the c-myb intronic NF-kappaB site upstream of a minimal promoter. 8-Br-cAMP and forskolin also increased the DNA binding activity of AP-1 complexes containing JunB, JunD and c-Fos in MEL cells which could cooperate with NF-kappaB. We conclude that inhibition of MEL cell differentiation by pharmacological doses of cAMP can be explained by the up-regulation of c-myb which is mediated, at least in part, by NF-kappaB p50/RelB heterodimers. |
| Databáze: | OpenAIRE |
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