MCB
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
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
Services
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 arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Osburn, D. L.
Right arrow Articles by Schulman, I. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Osburn, D. L.
Right arrow Articles by Schulman, I. G.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, August 2001, p. 4909-4918, Vol. 21, No. 15
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.15.4909-4918.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Ligand-Dependent Degradation of Retinoid X Receptors Does Not Require Transcriptional Activity or Coactivator Interactions

Deborah L. Osburn, Gang Shao,dagger H. Martin Seidel,Dagger and Ira G. Schulman*

Nuclear Receptor Discovery, Ligand Pharmaceuticals, San Diego, California 92121

Received 13 December 2000/Returned for modification 31 December 2000/Accepted 1 May 2001

Cells utilize ubiquitin-mediated proteolysis to regulate the activity of numerous proteins involved in signal transduction, cell cycle control, and transcriptional regulation. For a number of transcription factors, there appears to be a direct correlation between transcriptional activity and protein instability, suggesting that cells use targeted destruction as one method to down-regulate or attenuate gene expression. In this report we demonstrate that retinoid X receptors (RXRs) which function as versatile mediators of nuclear hormone-dependent gene expression are marked for destruction upon binding agonist ligands. Interestingly, when RXR serves as a heterodimeric partner for retinoic acid (RAR) or thyroid hormone (TR) receptors, binding of agonists by RAR or TR leads to degradation of both the transcriptionally active RAR or TR subunits as well as the transcriptionally inactive RXR subunit. Furthermore, using a series of mutants in the ligand-dependent activation domain (activation function 2), we demonstrate that agonist-stimulated degradation of RXR does not require corepressor release, coactivator binding, or transcriptional activity. Taken together, the data suggest a model for targeted destruction of transcription factors based on structural or conformational signals as opposed to functional coupling with gene transcription.

* Corresponding author. Present address: X-Ceptor Therapeutics, 4757 Nexus Center Dr., Suite 200, San Diego, CA 92121. Phone: (858) 458-4542. Fax: (858) 458-4501. E-mail: ischulman{at}x-ceptor.com.

dagger Present address: X-Ceptor Therapeutics, San Diego, CA 92121.

Dagger Present address: Dupont Pharmaceutical Research Laboratories, San Diego, CA 92121.

Molecular and Cellular Biology, August 2001, p. 4909-4918, Vol. 21, No. 15
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.15.4909-4918.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. J. Virol. Eukaryot. Cell
Microbiol. Mol. Biol. Rev. Clin. Vaccine Immunol. All ASM Journals

Copyright © 2001 by the American Society for Microbiology. All rights reserved.