![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 57, Issue 1, 82-92, January 2000
Department of Pharmacology, University of Kentucky Medical Center,
Lexington, Kentucky (S.E.H., H.I.S.); and Department of Biochemistry,
Medical University of South Carolina, Charleston, South Carolina
(R.S.P.)
The aryl hydrocarbon receptor (AhR) is a cytosolic basic
helix-loop-helix protein that associates with a chaperone complex that
includes two molecules of heat shock protein 90 (HSP90). It has been
hypothesized that after ligand binding, the AhR dissociates from its
chaperone complex and translocates into the nucleus, where it
heterodimerizes with its DNA binding partner, the AhR nuclear
translocator (ARNT), and activates specific genes. However, it remains
unclear whether nuclear translocation of the AhR occurs before or after
dissociation of the HSP90/chaperone complex. Because sodium molybdate
stabilizes the AhR-HSP90 interaction and inhibits the gene activation
of a number of steroid receptors, we reasoned that molybdate would be a
useful tool in delineating the role of HSP90 dissociation in AhR
nuclear translocation. In this study, we demonstrate that molybdate
inhibits AhR gene activation in both HepG2 and Hepa-1 cells in a
concentration-dependent manner and protects the AhR against
agonist-induced proteolysis. In addition, we demonstrate that AhR/ARNT
dimerization, but not nuclear translocation of the AhR, is inhibited by
molybdate. This indicates that 1) HSP90 dissociation is not required
for nuclear translocation of the AhR, 2) HSP90 dissociation is
essential for formation of the AhR/ARNT heterodimer, and 3) an
additional undefined regulatory step is required for AhR/ARNT
dimerization in the nucleus.
This article has been cited by other articles:
|
|
 |
|
  B. Platzer, S. Richter, D. Kneidinger, D. Waltenberger, M. Woisetschlager, and H. Strobl Aryl Hydrocarbon Receptor Activation Inhibits In Vitro Differentiation of Human Monocytes and Langerhans Dendritic Cells J. Immunol., July 1, 2009; 183(1): 66 - 74. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Soshilov and M. S. Denison Role of the Per/Arnt/Sim Domains in Ligand-dependent Transformation of the Aryl Hydrocarbon Receptor J. Biol. Chem., November 21, 2008; 283(47): 32995 - 33005. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. R. Evans, S. I. Karchner, L. L. Allan, R. S. Pollenz, R. L. Tanguay, M. J. Jenny, D. H. Sherr, and M. E. Hahn Repression of Aryl Hydrocarbon Receptor (AHR) Signaling by AHR Repressor: Role of DNA Binding and Competition for AHR Nuclear Translocator Mol. Pharmacol., February 1, 2008; 73(2): 387 - 398. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. M. Korashy and A. O. S. El-Kadi Regulatory Mechanisms Modulating the Expression of Cytochrome P450 1A1 Gene by Heavy Metals Toxicol. Sci., November 1, 2005; 88(1): 39 - 51. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Hoagland, E. M. Hoagland, and H. I. Swanson The p53 Inhibitor Pifithrin-{alpha} Is a Potent Agonist of the Aryl Hydrocarbon Receptor J. Pharmacol. Exp. Ther., August 1, 2005; 314(2): 603 - 610. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Martinez, S. J. Baek, D. M. Mays, P. K. Tithof, T. E. Eling, and N. J. Walker EGR1 Is a Novel Target for AhR Agonists in Human Lung Epithelial Cells Toxicol. Sci., December 1, 2004; 82(2): 429 - 435. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Joiakim, P. A. Mathieu, A. A. Elliott, and J. J. Reiners Jr. Superinduction of CYP1A1 in MCF10A Cultures by Cycloheximide, Anisomycin, and Puromycin: A Process Independent of Effects on Protein Translation and Unrelated to Suppression of Aryl Hydrocarbon Receptor Proteolysis by the Proteasome Mol. Pharmacol., October 1, 2004; 66(4): 936 - 947. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. H. Black and L. C. Quattrochi MOLECULAR CLONING OF THE GUINEA PIG CYP1A2 GENE 5'-FLANKING REGION: IDENTIFICATION OF FUNCTIONAL AROMATIC HYDROCARBON RESPONSE ELEMENT AND CHARACTERIZATION OF CYP1A2 EXPRESSION IN GPC16 CELLS Drug Metab. Dispos., June 1, 2004; 32(6): 595 - 602. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Joiakim, P. A. Mathieu, C. Palermo, T. A. Gasiewicz, and J. J. Reiners Jr. THE JUN N-TERMINAL KINASE INHIBITOR SP600125 IS A LIGAND AND ANTAGONIST OF THE ARYL HYDROCARBON RECEPTOR Drug Metab. Dispos., November 1, 2003; 31(11): 1279 - 1282. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Saydam, F. Steiner, O. Georgiev, and W. Schaffner Heat and Heavy Metal Stress Synergize to Mediate Transcriptional Hyperactivation by Metal-responsive Transcription Factor MTF-1 J. Biol. Chem., August 22, 2003; 278(34): 31879 - 31883. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Petrulis, A. Kusnadi, P. Ramadoss, B. Hollingshead, and G. H. Perdew The hsp90 Co-chaperone XAP2 Alters Importin beta Recognition of the Bipartite Nuclear Localization Signal of the Ah Receptor and Represses Transcriptional Activity J. Biol. Chem., January 17, 2003; 278(4): 2677 - 2685. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. Woods and M. L. Whitelaw Differential Activities of Murine Single Minded 1 (SIM1) and SIM2 on a Hypoxic Response Element. CROSS-TALK BETWEEN BASIC HELIX-LOOP-HELIX/Per-Arnt-Sim HOMOLOGY TRANSCRIPTION FACTORS J. Biol. Chem., March 15, 2002; 277(12): 10236 - 10243. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Gambone, J. M. Hutcheson, J. L. Gabriel, R. L. Beard, R. A.S. Chandraratna, K. J. Soprano, and D. R. Soprano Unique Property of Some Synthetic Retinoids: Activation of the Aryl Hydrocarbon Receptor Pathway Mol. Pharmacol., February 1, 2002; 61(2): 334 - 342. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Heid, M. K. Walker, and H. I. Swanson Correlation of Cardiotoxicity Mediated by Halogenated Aromatic Hydrocarbons to Aryl Hydrocarbon Receptor Activation Toxicol. Sci., May 1, 2001; 61(1): 187 - 196. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Pollenz and E. R. Barbour Analysis of the Complex Relationship between Nuclear Export and Aryl Hydrocarbon Receptor-Mediated Gene Regulation Mol. Cell. Biol., August 15, 2000; 20(16): 6095 - 6104. [Abstract] [Full Text]
|
|
|
|
|
|
J. R. Petrulis, N. G. Hord, and G. H. Perdew Subcellular Localization of the Aryl Hydrocarbon Receptor Is Modulated by the Immunophilin Homolog Hepatitis B Virus X-associated Protein 2 J. Biol. Chem., November 22, 2000; 275(48): 37448 - 37453. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kazlauskas, L. Poellinger, and I. Pongratz The Immunophilin-like Protein XAP2 Regulates Ubiquitination and Subcellular Localization of the Dioxin Receptor J. Biol. Chem., December 22, 2000; 275(52): 41317 - 41324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Baba, J. Mimura, K. Gradin, A. Kuroiwa, T. Watanabe, Y. Matsuda, J. Inazawa, K. Sogawa, and Y. Fujii-Kuriyama Structure and Expression of the Ah Receptor Repressor Gene J. Biol. Chem., August 24, 2001; 276(35): 33101 - 33110. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
