1. Sponsor Organization: NIH/NIEHS

2. Project Title: 04869-10 REGULATION OF THE AH RECEPTOR

3. Project Focus:

• Project Primary Focus: Human Health Effects
• Project Secondary Focus:

4. Description:

The multiple mechanisms of AhR regulation will be examined along with elucidation of the biochemical events from initial synthesis and assembly to translocation into the nucleus. Using an in vitro translation system the 90 kDa heat shock protein (hsp90) binding site on the AhR will be determined using a series of truncation and deletion cDNA mutants. The location of the binding site(s) will be compared with the DNA binding, dimerization, ligand binding, and transactivation domains to gain insight into the functional significance of this protein/protein interaction. The protein composition of the 9S cytosolic form of the AhR in Hepa 1 cells will be determined by immunoprecipitation with antibodies raised against specific AhR peptide sequences. Both chemically crosslinked and non-crosslinked AhR will be characterized on western blots using antibodies to the AhR, Arnt, and hsp90. The intracellular location of the unliganded and liganded AhR in Hepa 1 cells will be determined using immunocytochemical techniques and one- and two-dimensional nonfocal microscopy. The protein and cofactor requirements (e.g. ATP, hsp70, Arnt) for nuclear localization/translocation will be determined using a permeabilized cell system.

5. References:

6. Inventory Category:

• Primary: Models
• Secondary:

7. Inventory Subcategory:

• Primary: Basic Research
• Secondary:

8. Keywords for Experimental System/Species:

• Species:
• Study Type:
  • In Vitro
  • Laboratory Study
• Fate and Transport:

9. Keywords for Experimental Endpoints:

• Health Effect:
  • Ah Receptor
• Hormonal Measures:
• Level Of Study:
• Chemistry Metabolism:
• Life Stage:
• Risk Assessment:

10. Chemical Agents:

• Dioxins

11. Performing Institution:

• PENNSYLVANIA STATE UNIVERSITY-UNIV PARK

12. Contact:

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