Document Detail

cAMP-induced NF-kappaB (p50/relB) binding to a c-myb intronic enhancer correlates with c-myb up-regulation and inhibition of erythroleukemia cell differentiation.
MedLine Citation:
PMID:  9362453     Owner:  NLM     Status:  MEDLINE    
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.
M Suhasini; C D Reddy; E P Reddy; J A DiDonato; R B Pilz
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Oncogene     Volume:  15     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  1997 Oct 
Date Detail:
Created Date:  1997-12-04     Completed Date:  1997-12-04     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1859-70     Citation Subset:  IM    
Department of Medicine and Cancer Centre, University of California, San Diego, La Jolla 92093, USA.
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MeSH Terms
Cell Differentiation / genetics*
Cyclic AMP / analogs & derivatives,  pharmacology*
Enhancer Elements, Genetic*
Forskolin / pharmacology
Genes, Reporter
Leukemia, Erythroblastic, Acute / genetics*,  metabolism,  pathology
NF-kappa B / metabolism*
Protein Binding
RNA, Messenger / genetics,  metabolism
Subcellular Fractions / metabolism
Transcription Factors / metabolism
Tumor Cells, Cultured
Reg. No./Substance:
0/NF-kappa B; 0/RNA, Messenger; 0/Transcription Factors; 60-92-4/Cyclic AMP; 66428-89-5/Forskolin

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