Document Detail


c-Myb trans-activates the human DNA topoisomerase IIalpha gene promoter.
MedLine Citation:
PMID:  9045645     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
DNA topoisomerase IIalpha (topo IIalpha) is an essential proliferation-dependent nuclear enzyme which has been exploited as an anti-tumor drug target. Since the proliferative status of human leukemia cells is associated with expression of the c-myb proto-oncogene, c-Myb was investigated as a trans-activator of the topo IIalpha gene. Using topo IIalpha promoter-luciferase reporter plasmids, c-myb expression caused trans-activation of the topo IIalpha promoter a maximum of approximately 4.5-fold over basal levels in HL-60 human promyelocytic leukemia cells. Trans-activation was submaximal with higher levels of c-myb expression plasmid but a Myb protein lacking its negative regulatory domain resulted in approximately 19-fold trans-activation. Mutagenesis and 5'-deletion studies revealed that Myb trans-activation was mediated via a Myb-binding site at positions -16 to -11 and that this region governed the bulk of basal topo IIalpha promoter activity in human leukemia cells. Trans-activation of topo IIalpha by c-Myb was lymphoid- or myeloid-dependent. However, B-Myb, a more widely-expressed Myb family member, caused topo IIalpha trans-activation in both HL-60 cells and HeLa epithelial cervical carcinoma cells. These data provide evidence for a new Myb-responsive gene which is directly linked to and required for cellular proliferation.
Authors:
T L Brandt; D J Fraser; S Leal; P M Halandras; A R Kroll; D J Kroll
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  272     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1997 Mar 
Date Detail:
Created Date:  1997-04-14     Completed Date:  1997-04-14     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  6278-84     Citation Subset:  IM    
Affiliation:
Department of Pharmaceutical Sciences, University of Colorado School of Pharmacy and the University of Colorado Cancer Center, Denver, Colorado 80262, USA.
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MeSH Terms
Descriptor/Qualifier:
Cell Division
DNA Topoisomerases, Type II / genetics*
Gene Expression Regulation, Enzymologic*
HL-60 Cells
Hela Cells
Humans
Promoter Regions, Genetic*
Proto-Oncogene Proteins / physiology*
Proto-Oncogene Proteins c-myb
Sequence Deletion
Trans-Activators / physiology*
Transcriptional Activation*
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
GM50381/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-myb; 0/Trans-Activators; EC 5.99.1.3/DNA Topoisomerases, Type II

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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