title: A cAMP-regulatory sequence (CRS1) of CYP17 is a cellular target for the homeodomain protein Pbx1.
abstract: Cytochrome P450c17 encoded by CYP17, whose expression is regulated by peptide hormones via cAMP, is required for cortisol and sex hormone biosynthesis thereby playing a key role in biological processes including sexual differentiation. Utilizing the cAMP-regulatory sequence CRS1 of the bovine CYP17 gene as an affinity ligand, four CRS1-binding proteins 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 established two of them to be the homeodomain proteins Pbx1a and Pbx1b, originally discovered by their involvement in the t(1;19) chromosomal translocation in pre-B-cell acute lymphoblastic leukemias. Overexpression of Pbx1 in Y1 cells enhances cAMP-dependent transcription of the CRS1-dependent reporter gene. These results identify the CRS1 of bovine CYP17 as a cellular target for Pbx1 and suggest that one role of this homeodomain protein is in the regulation of steroidogenesis and subsequently sexual development.
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146.
authors.forename: N
authors.initials: N
authors.lastname: Kagawa
authors.forename: A
authors.initials: A
authors.lastname: Ogo
authors.forename: Y
authors.initials: Y
authors.lastname: Takahashi
authors.forename: A
authors.initials: A
authors.lastname: Iwamatsu
authors.forename: M R
authors.initials: MR
authors.lastname: Waterman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D005801:Genes, Homeobox; D051379:Mice; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000737:chemistry; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D015345:Oligonucleotide Probes; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C083400:PBX1 protein, human; D013254:Steroid 17-alpha-Hydroxylase