Document Detail


Transcriptional elongation of c-myb is regulated by NF-kappaB (p50/RelB).
MedLine Citation:
PMID:  10602492     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
High levels of c-myb expression are necessary for the proliferation of hematopoietic precursor cells whereas down-regulation of c-myb is required for terminal differentiation; this down-regulation occurs through a conditional block to transcriptional elongation in intron I. We previously observed that cAMP analogs prevented the late down-regulation of c-myb during hexamethylene bisacetamide (HMBA)-induced differentiation of murine erythroleukemia (MEL) cells and blocked differentiation; this correlated with the induction of NF-kappaB (p50/RelB) complexes which were shown to bind to NF-kappaB recognition sites flanking the transcriptional pause site of c-myb. We now selected stably-transfected MEL cells which overexpressed p50, RelB or both at levels similar to those induced by cAMP to determine whether these NF-kappaB proteins regulate c-myb expression in intact cells. We demonstrate that transcriptionally active NF-kappaB (p50/RelB) complexes, but not p50 or RelB alone, prevented the early and late down-regulation of c-myb mRNA and increased c-myb transcriptional elongation in HMBA-induced MEL cells. The increase in c-myb expression was sufficient to block erythroid differentiation and allow continuous proliferation of cells in the presence of HMBA. Steady-state c-myb mRNA levels in untreated cells were not affected by overexpression of NF-kappaB, suggesting that p50/RelB specifically modulated the efficiency of transcriptional attenuation during MEL cell differentiation.
Authors:
M Suhasini; R B Pilz
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Oncogene     Volume:  18     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  1999 Dec 
Date Detail:
Created Date:  2000-01-06     Completed Date:  2000-01-06     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  7360-9     Citation Subset:  IM    
Affiliation:
Department of Medicine and Cancer Center, University of California, San Diego, La Jolla, California, CA 92037-0652, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Differentiation / genetics
Cell Division / genetics
Genes, myb*
Hematopoietic Stem Cells / pathology,  physiology
Leukemia, Erythroblastic, Acute
Mice
NF-kappa B / genetics*
Transcription, Genetic*
Transcriptional Activation*
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
R01-GM55586/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/NF-kappa B

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