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PMID: 9115370 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Transcription factor Sp3 antagonizes activation of the ornithine decarboxylase promoter by Sp1.

Nucleic acids research ·Vol. 25 ·No. 10 ·1997-05-15 ·Pages 2012-9

Kumar AP, Butler AP

Abstract

Ornithine decarboxylase (ODC) expression is important for proliferation and is elevated in many tumor cells. We previously showed that Sp1 is a major positive regulator of ODC transcription. In this paper we have investigated transcriptional regulation of rat ODC by the closely related factor Sp3. While over-expression of Sp1 caused a dramatic activation of the ODC promoter, over-expression of Sp3 caused little or no activation in either Drosophila SL2 cells (lacking endogenous Sp1 or Sp3) or in H35 rat hepatoma cells. Furthermore, co-transfection studies demonstrated that Sp3 abolished trans -activation of the ODC promoter by Sp1. DNase I footprint studies and electrophoretic mobility shift assays demonstrated that both recombinant Sp1 and Sp3 bind specifically to several sites within the ODC promoter also protected by nuclear extracts, including overlapping GC and CT motifs located between -116 and -104. This CT element is a site of negative ODC regulation. Mutation of either element reduced binding, but mutation of both sites was required to eliminate binding of either Sp1 or Sp3. These results demonstrate that ODC is positively regulated by Sp1 and negatively regulated by Sp3, suggesting that the ratio of these transcription factors may be an important determinant of ODC expression during development or transformation.

MeSH Terms
Animals Base Sequence Cell Nucleus/metabolism Cloning, Molecular DNA Footprinting DNA Mutational Analysis DNA-Binding Proteins/metabolism Deoxyribonuclease I Escherichia coli Gene Expression Regulation, Enzymologic Glutathione Transferase/biosynthesis Kinetics Liver Neoplasms, Experimental Luciferases/biosynthesis Oligodeoxyribonucleotides Ornithine Decarboxylase/biosynthesis,genetics Promoter Regions, Genetic Rats Recombinant Fusion Proteins/biosynthesis Sp1 Transcription Factor/metabolism Sp3 Transcription Factor Transcription Factors/metabolism Transcription, Genetic Transfection Tumor Cells, Cultured Zinc Fingers
Chemicals
DNA-Binding Proteins Oligodeoxyribonucleotides Recombinant Fusion Proteins Sp1 Transcription Factor Sp3 protein, rat Transcription Factors Sp3 Transcription Factor Luciferases Glutathione Transferase Deoxyribonuclease I Ornithine Decarboxylase
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Kumar A P
The University of Texas M. D. Anderson Cancer Center, Science Park-Research Division, Smithville, TX 78957, USA.
Butler A P
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
0305-1048
DOI
10.1093/nar/25.10.2012
Published
1997-05-15
Pages
2012-9
Language
English
Region
England
NLM ID
0411011
PMCID
PMC146696
Subset
IM
Grants
NCI NIH HHS · CA 46629 · United States
External Links
PubMed source DOI: 10.1093/nar/25.10.2012 PMC Full Text View journal details
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