A cAMP-regulatory sequence (CRS1) of CYP17 is a cellular target for the homeodomain protein Pbx1

J Biol Chem. 1994 Jul 22;269(29):18716-9.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cattle
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation
  • Genes, Homeobox*
  • Mice
  • Molecular Sequence Data
  • Oligonucleotide Probes / chemistry
  • Pre-B-Cell Leukemia Transcription Factor 1
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / metabolism*
  • RNA, Messenger / genetics
  • Regulatory Sequences, Nucleic Acid
  • Steroid 17-alpha-Hydroxylase / genetics*

Substances

  • DNA-Binding Proteins
  • Oligonucleotide Probes
  • Pre-B-Cell Leukemia Transcription Factor 1
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • pbx1 protein, human
  • Steroid 17-alpha-Hydroxylase

Associated data

  • GENBANK/L27453