JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lee, M.-O.
Right arrow Articles by Pfahl, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lee, M.-O.
Right arrow Articles by Pfahl, M.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Volume 271, Number 20, Issue of May 17, 1996 pp. 11897-11903
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
A Novel Class of Retinoid Antagonists and Their Mechanism of Action

(Received for publication, September 25, 1995; and in revised form, February 20, 1996)

Mi-Ock Lee,  Marcia I. Dawson ,  Nathalie Picard,  Peter D. Hobbs ,  Magnus Pfahl

Retinoids regulate a broad range of biological processes through two subfamilies of nuclear retinoid receptors, the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs). Recently, we reported a novel type of retinoic acid antagonist (SR11335) and showed that this compound can inhibit retinoic acid (RA)-induced activation of a human immunodeficiency virus type 1 (HIV-1) promoter construct that contains a special RA response element (RARE). We have now further characterized the antagonism mediated by SR11335 and of newly synthesized structurally related compounds. Two compounds, SR11330 and SR11334, which are poor transactivators, also showed antagonist activities, inhibiting all-trans-RA (tRA) and 9-cis-RA. The retinoids inhibited transcriptional activation of RAR/RXR heterodimers effectively,while inhibition of RXR homodimers was less efficient. Inhibition was observed on several RAREs, including the TREpal, betaRARE, apoAI-RARE,and CRBPI-RARE. In addition, the antagonists inhibited tRA-induced differentiation of HL-60 cells. The antagonist did not interfere with DNA binding of the receptors. In limited proteolytic digestion assays, SR11335 induced resistance of the receptors to proteolysis, but the pattern of the degradation was not altered from that induced by tRA, suggesting that these antagonists induce their biological effects by competing with agonists for binding to RARs, thereby preventing the induction of conformational changes of the receptors necessary for transcriptional activation.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 J Mol EndocrinolHome page
J. Nevado, S. P Tenbaum, A. I. Castillo, A. Sanchez-Pacheco, and A. Aranda
Activation of the human immunodeficiency virus type I long terminal repeat by 1{alpha},25-dihydroxyvitamin D3
J. Mol. Endocrinol., June 1, 2007; 38(6): 587 - 601.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
T. M. Hanley, H. L. B. Kiefer, A. C. Schnitzler, J. E. Marcello, and G. A. Viglianti
Retinoid-Dependent Restriction of Human Immunodeficiency Virus Type 1 Replication in Monocytes/Macrophages
J. Virol., March 15, 2004; 78(6): 2819 - 2830.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
D. R. Soprano and K. J. Soprano
Pharmacological Doses of Some Synthetic Retinoids Can Modulate Both the Aryl Hydrocarbon Receptor and Retinoid Receptor Pathways
J. Nutr., January 1, 2003; 133(1): 277S - 281.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. Ozono, M. Saito, D. Miura, T. Michigami, S. Nakajima, and S. Ishizuka
Analysis of the Molecular Mechanism for the Antagonistic Action of a Novel 1alpha ,25-Dihydroxyvitamin D3 Analogue toward Vitamin D Receptor Function
J. Biol. Chem., November 5, 1999; 274(45): 32376 - 32381.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
N. Ferrari, M. Pfahl, and G. Levi
Retinoic Acid Receptor gamma 1 (RARgamma 1) Levels Control RARbeta 2 Expression in SK-N-BE2(c) Neuroblastoma Cells and Regulate a Differentiation-Apoptosis Switch
Mol. Cell. Biol., November 1, 1998; 18(11): 6482 - 6492.
[Abstract] [Full Text]

Home page
 J. Virol.Home page
A. Angulo, R. A. S. Chandraratna, J. F. LeBlanc, and P. Ghazal
Ligand Induction of Retinoic Acid Receptors Alters an Acute Infection by Murine Cytomegalovirus
J. Virol., June 1, 1998; 72(6): 4589 - 4600.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Scafonas, C. L. Wolfgang, J. L. Gabriel, K. J. Soprano, and D. R. Soprano
Differential Role of Homologous Positively Charged Amino Acid Residues for Ligand Binding in Retinoic Acid Receptor alpha Compared with Retinoic Acid Receptor beta
J. Biol. Chem., April 25, 1997; 272(17): 11244 - 11249.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. S. Klein, J. W. Wang, B. Khalifa, S. A. Gavigan, and R. A. S. Chandraratna
Recruitment of Nuclear Receptor Corepressor and Coactivator to the Retinoic Acid Receptor by Retinoid Ligands. INFLUENCE OF DNA-HETERODIMER INTERACTIONS
J. Biol. Chem., June 16, 2000; 275(25): 19401 - 19408.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 1996 by the American Society for Biochemistry and Molecular Biology.