ISSN:
1423-0127
Keywords:
Promoter
;
Transcription factor
;
Transactivation
;
Signal transduction
;
Phorbol ester
;
Protein kinase A
;
Protein kinase C
;
DNA repair enzyme
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
,
Medicine
Notes:
Abstract That mammalian DNA polymerase-β (β-pol) gene transcription is upregulated by activatedras and also by phorbol ester (TPA) treatment suggests the involvement of protein kinase C in the gene expression control for this DNA repair enzyme. Yet, the core promoters of the human, bovine and rodent β-pol genes do not have a TPA response element or other binding site for the transcriptional activator AP-1. Instead, these β-pol promoters appear to be regulated mainly by proteins binding to the cAMP response element (CRE) centered within 50 bp 5′ of the transcriptional start site. In this study, the CRE in the human β-pol promoter was found to mediate TPA upregulation of the cloned promoter in HeLa cell transient expression experiments. To further examine the role of this CRE in TPA stimulation, we used several mutated promoters that were either deficient in protein binding to the CRE or contained extra CRE sites arranged as tandem repeats. All constructs with at least one functional CRE were upregulated by TPA, whereas mutants lacking CRE protein-binding function were not TPA upregulated. Analyses of HeLa nuclear extract DNA-binding proteins indicated that the β-pol CRE was bound by CRE-binding protein (CREB) family members CREB-1 and activating transcription factor-1, but not by AP-1 or complexes containg AP-1 subunits. These results suggest that CREB, rather than AP-1 proteins, are required for the CRE-mediated TPA activation of the β-pol promoter.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF02258351
Permalink
