The DBP transcriptional activation domain is highly homologous to that of HLF and TEF and is not responsible for the tissue type-specific transcriptional activity of DBP.
DBP, HLF and TEF comprise a distinct subfamily of mammalian bZIP proteins that plays an important role in regulation of tissue-specific gene expression, particularly in the liver. In this report we demonstrate that DBP contains a 38 amino acid TAD which is highly homologous to the HLF and TEF TADs that we have delineated previously. Deletion of this domain completely abrogates transcriptional activity of native DBP and GAL4-DBP fusion proteins. This domain functions as a modular TAD that is a potent transcriptional activator when fused to the GAL4 DBD. While DBP itself is a liver-specific transactivator, the DBP TAD is active in a variety of cell types, indicating that liver-specific activity is not an intrinsic property of the TAD and must be conferred by other regions of the protein. Using GAL4-HLF fusion proteins, we further refine the core TAD of PAR proteins to a region of 13 amino acids. Recently described PAR-bZIP proteins from Drosophila and zebrafish also contain domains that share strong homology with the TAD of mammalian PAR proteins, making this one of the most highly evolutionarily conserved TADs identified to date.
Section of Pediatric Hematology/Oncology, University of Colorado Cancer Center and School of Medicine, 4200 East Ninth Ave., Denver, CO 80262, USA.
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D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors; D001665:Binding Sites / Q000235:genetics; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D004274:DNA, Recombinant; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D029961:Zebrafish Proteins
D050976:Basic-Leucine Zipper Transcription Factors; C063898:DBP protein, human; D004274:DNA, Recombinant; D004268:DNA-Binding Proteins; C498260:Dbp protein, mouse; C490671:HLF protein, human; C490670:Hlf protein, mouse; D011993:Recombinant Fusion Proteins; C489490:TEF protein, human; C489491:Tef protein, mouse; D014157:Transcription Factors; D029961:Zebrafish Proteins; C489492:tefa protein, zebrafish; D015500:Chloramphenicol O-Acetyltransferase