A heterodimeric nuclear protein complex binds two palindromic sequences in the proximal enhancer of the human erbB-2 gene.
Increased expression of the protein-tyrosine kinase receptor ErbB-2 occurs frequently in human breast and ovarian cancer and causes transformation in experimental systems. Control of transcription of the erbB-2 gene is an important determinant of receptor expression. Within the human erbB-2 promoter, a 100-base pair (bp) region 5' to the TATA box enhances transcription 200-fold. Two palindromes present in this 100-bp region are important for both positive and negative transcriptional control. A nuclear palindrome binding protein (PBP) has been purified to near homogeneity using ion-exchange, DNA-affinity, and gel filtration chromatography. PBP is a heterodimer consisting of a 69-kDa alpha subunit that binds DNA and a 60-kDa beta subunit that appears to enhance subunit binding. DNase I footprinting and electrophoretic mobility shift assays indicate that PBP binds to the half-site of each palindrome with the core recognition sequence TGGGAG. By DNA binding specificity and lack of immunological cross-reactivity, PBP is distinct from NF-kappaB and Ikaros, two proteins with related DNA binding specificities. PBP is proposed to be an important regulator of transcription of the erbB-2 gene.
Chen
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Department of Biology, University of California at San Diego, La Jolla, 92093-0650, USA.
Gill
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D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D002846:Chromatography, Affinity; D002848:Chromatography, DEAE-Cellulose; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D004742:Enhancer Elements, Genetic; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D018734:Genes, erbB-2; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009687:Nuclear Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism; D013724:Teratoma; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides