title: Regulation of the DBP promoter by PAR proteins and in leukemic cells bearing an E2A/HLF translocation.
abstract: The D-site binding protein (DBP) is a member of the PAR domain subfamily of b/ZIP proteins, whose expression in the liver is highly sensitive to the growth state of that organ. This paper examines the regulation of the DBP promoter by C/EBP alpha and examines the role of autoregulation in its expression. Of four previously characterized proximal promoter sites, sites I and III are shown to bind C/EBP alpha, but cotransfection in Hep G2 cells of a C/EBP alpha expression vector is unable to transactivate the promoter. In contrast, the expression of DBP, particularly in conjunction with the related protein HLF, is able to dramatically upregulate expression directed by the proximal promoter. Deletion analysis and the use of single site reporter constructs demonstrate that sites II and IV are highly responsive to transactivation by DBP and HLF. The DBP promoter is active in the UOC-B1 cell line, which bears a 17:19 translocation resulting in the creation of an E2A:HLF fusion protein. The proteins binding to site IV are elevated in this line, suggesting that upregulation of DBP expression in response to inappropriate HLF activity may be mediated through this site.
authors.affiliation: Cancer Research Laboratories, Queen's University, Kingston, Ontario, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Newcombe
authors.forename: T
authors.initials: T
authors.lastname: Glassco
authors.forename: C
authors.initials: C
authors.lastname: Mueller
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology; D051790:G-Box Binding Factors; D005786:Gene Expression Regulation / Q000235:genetics*; D017930:Genes, Reporter / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D017384:Sequence Deletion / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D014158:Transcription, Genetic / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics; D014162:Transfection / Q000235:genetics; D014178:Translocation, Genetic / Q000235:genetics*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000502:physiology
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D022762:CCAAT-Enhancer-Binding Proteins; C485975:DBP protein, rat; D004268:DNA-Binding Proteins; D051790:G-Box Binding Factors; C490671:HLF protein, human; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; C095828:Hlf protein, rat