A CAMP-REGULATORY SEQUENCE (CRS1) OF CYP17 IS A CELLULAR TARGET FOR THE HOMEODOMAIN PROTEIN PBX1

Cytochrome P450c17 encoded by CYP17, whose expression is regulated by peptide hormones via cAMP, is required for cortisol and sex hormone bi osynthesis thereby playing a key role in biological processes includin g sexual differentiation. Utilizing the cAMP-regulatory sequence CRS1 of the bovine CYP17 gene as an affinity ligand, four CRS1-binding prot eins have been purified from nuclear extracts of mouse adrenocortical Y1 cells and shown to enhance the in vitro transcription of a reporter gene promoted by CRS1. Microsequencing of these four proteins establi shed two of them to be the homeodomain proteins Pbx1a and Pbx1b, origi nally discovered by their involvement in the t(1;19) chromosomal trans location in pre-B-cell acute lymphoblastic leukemias. Overexpression o f Pbx1 in Y1 cells enhances cAMP-dependent transcription of the CRS1-d ependent reporter gene. These results identify the CRS1 of bovine CYP1 7 as a cellular target for Pbx1 and suggest that one role of this home odomain protein is in the regulation of steroidogenesis and subsequent ly sexual development.