New Investigator Award

Abstract

The Ah-receptor is a soluble protein which regulates the expression of a number of genes encoding enzymes involved in the metabolism of foreign compounds (e.g., cytochrome-P450s, glutathione S-transferases, quinone reductases, etc). In response to potent agonists, such as 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD), the Ah-receptor also mediates a variety of toxic responses, including epithelial hyperplasia and metaplasia, lymphoid involution, tumor promotion and teratogenesis. Our recent cloning of the Ah- receptor cDNA has demonstrated that this receptor is a member of a newly discovered family of transcription factors characterized by an N-terminal helix- loop helix motif and an adjacent domain responsible for ligand binding (in the Ah-receptor) and with unknown function in other family members (i.e., Sim, Per and Arnt proteins). Research in my laboratory can be divided in to two major areas of emphasis; (1) understanding the mechanism by which the Ah-receptor mediates the toxicity of halogenated aromatic compounds like TCDD and (2) determining the risk that compounds like TCDD pose to human and wildlife populations. As an initial step in reaching these objectives, we have purified the Ah-receptor to homogeneity, sequenced the proteins N-terminus, raised antibodies against a synthetic peptide corresponding to this sequence, cloned the Ah-receptor cDNA from both mouse and human and cloned and characterized the murine structural gene.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Nov 30, 1992
Accession Number
ADA266249

Entities

People

  • Joan Cassendy

Organizations

  • Society of Toxicology

Tags

DTIC Thesaurus Topics

  • Air Force
  • Amino Acids
  • Antibodies
  • Aromatic Compounds
  • Blood Coagulation Factors
  • Cells
  • Chemistry
  • Coding
  • Human Population
  • Immune Serums
  • Peptides
  • Proteins
  • Sensitivity
  • Sequences
  • Tissue Extracts
  • Transcription Factors
  • Transferases

Readers

  • Molecular Biology and Genetics
  • Molecular Genetics
  • Molecular and Cellular Biochemistry