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.