PMID- 11438648
OWN - NLM
STAT- MEDLINE
DCOM- 20010816
LR  - 20181113
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 21
IP  - 15
DP  - 2001 Aug
TI  - Ligand-dependent degradation of retinoid X receptors does not require 
      transcriptional activity or coactivator interactions.
PG  - 4909-18
AB  - 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.
FAU - Osburn, D L
AU  - Osburn DL
AD  - Nuclear Receptor Discovery, Ligand Pharmaceuticals, San Diego, California 92121, 
      USA.
FAU - Shao, G
AU  - Shao G
FAU - Seidel, H M
AU  - Seidel HM
FAU - Schulman, I G
AU  - Schulman IG
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Ligands)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Receptors, Thyroid Hormone)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Transcription Factors)
RN  - 0 (Ubiquitins)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cell Line
MH  - Cell Nucleus/metabolism
MH  - Cells, Cultured
MH  - Dimerization
MH  - Enzyme Activation
MH  - Ligands
MH  - Mutation
MH  - Plasmids/metabolism
MH  - Precipitin Tests
MH  - Protein Binding
MH  - Protein Conformation
MH  - Protein Structure, Tertiary
MH  - Receptors, Retinoic Acid/*metabolism
MH  - Receptors, Thyroid Hormone/metabolism
MH  - Retinoid X Receptors
MH  - Signal Transduction
MH  - Time Factors
MH  - Transcription Factors/*metabolism
MH  - *Transcription, Genetic
MH  - Transcriptional Activation
MH  - Transfection
MH  - Ubiquitins/metabolism
PMC - PMC87210
EDAT- 2001/07/05 10:00
MHDA- 2001/08/17 10:01
PMCR- 2001/08/01
CRDT- 2001/07/05 10:00
PHST- 2001/07/05 10:00 [pubmed]
PHST- 2001/08/17 10:01 [medline]
PHST- 2001/07/05 10:00 [entrez]
PHST- 2001/08/01 00:00 [pmc-release]
AID - 2074 [pii]
AID - 10.1128/MCB.21.15.4909-4918.2001 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2001 Aug;21(15):4909-18. doi: 10.1128/MCB.21.15.4909-4918.2001.