The homeodomain protein Pbx1 is involved in cAMP-dependent transcription of human CYP17.

Ogo A, Waterman MR, McAllister JM, Kagawa N
Arch Biochem Biophys. 1997 348 (1): 226-31

PMID: 9390195 · DOI:10.1006/abbi.1997.0372

Pbx1 is a homeodomain transcription factor involved in cAMP-dependent transcriptional regulation of the bovine CYP17 gene. In this study, we have investigated the involvement of Pbx1 in the transcriptional regulation of the human CYP17 gene. Although a sequence identical to previously determined Pbx-binding sites is not present in the promoter region of the human CYP17 gene, three putative Pbx-binding sites are identified by sequence similarity analysis. Coexpression of Pbx1 and a catalytic subunit of protein kinase A (PKA) greatly enhances reporter gene transcription via the 5'-flanking region of the human CYP17 gene. Upon gel shift analysis utilizing nuclear extracts from human adrenal H295R cells, one of the three putative Pbx1-binding sites, -250/-241 bp, shows the typical intense doublet observed with other Pbx-binding sites. 5'-Deletion analyses of the reporter construct containing this Pbx-binding site showed approximately sixfold induction by coexpression of Pbx1 and PKA compared to the basal transcription, suggesting that Pbx1 binds the -250/-241 bp sequence and participates in cAMP-dependent regulation of the human CYP17 gene.

MeSH Terms (25)

Adrenal Glands Animals Base Sequence Binding Sites Cattle Cell Line Consensus Sequence Cyclic AMP Cyclic AMP-Dependent Protein Kinases DNA-Binding Proteins Genes, Reporter Homeodomain Proteins Humans Luciferases Oligodeoxyribonucleotides Pre-B-Cell Leukemia Transcription Factor 1 Promoter Regions, Genetic Proto-Oncogene Proteins Recombinant Fusion Proteins Sequence Deletion Steroid 17-alpha-Hydroxylase Transcription, Genetic Transcriptional Activation Transfection Tumor Cells, Cultured

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