Abstract
Estrogen receptor-α (ERα) is downregulated in the presence of its cognate ligand, estradiol (E2), through the ubiquitin proteasome pathway. Here, we show that ubiquitin proteasome function is required for ERα to serve as a transcriptional activator. Deletion of the last 61 amino acids of ERα, including residues that form helix 12, abolishes ligand-mediated downregulation of the receptor as do point mutations in the ligand binding domain that impair coactivator binding. In addition, coactivators also are subject to degradation by the 26S proteasome, but their intrinsic transcriptional activity is not affected. These data provide evidence that protein interactions with ERα coactivator binding surfaces are important for ligand-mediated receptor down-regulation and suggest that receptor and coactivator turnover contributes to ERα transcriptional activity.
| Original language | English |
|---|---|
| Pages (from-to) | 939-948 |
| Number of pages | 10 |
| Journal | Molecular Cell |
| Volume | 5 |
| Issue number | 6 |
| State | Published - Dec 28 2000 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Molecular Biology
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The 26S proteasome is required for estrogen receptor-α and coactivator turnover and for efficient estrogen receptor-α transactivation. / Lonard, David M.; Nawaz, Zafar; Smith, Carolyn L.; O'Malley, Bert W.
In: Molecular Cell, Vol. 5, No. 6, 28.12.2000, p. 939-948.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The 26S proteasome is required for estrogen receptor-α and coactivator turnover and for efficient estrogen receptor-α transactivation
AU - Lonard, David M.
AU - Nawaz, Zafar
AU - Smith, Carolyn L.
AU - O'Malley, Bert W.
PY - 2000/12/28
Y1 - 2000/12/28
N2 - Estrogen receptor-α (ERα) is downregulated in the presence of its cognate ligand, estradiol (E2), through the ubiquitin proteasome pathway. Here, we show that ubiquitin proteasome function is required for ERα to serve as a transcriptional activator. Deletion of the last 61 amino acids of ERα, including residues that form helix 12, abolishes ligand-mediated downregulation of the receptor as do point mutations in the ligand binding domain that impair coactivator binding. In addition, coactivators also are subject to degradation by the 26S proteasome, but their intrinsic transcriptional activity is not affected. These data provide evidence that protein interactions with ERα coactivator binding surfaces are important for ligand-mediated receptor down-regulation and suggest that receptor and coactivator turnover contributes to ERα transcriptional activity.
AB - Estrogen receptor-α (ERα) is downregulated in the presence of its cognate ligand, estradiol (E2), through the ubiquitin proteasome pathway. Here, we show that ubiquitin proteasome function is required for ERα to serve as a transcriptional activator. Deletion of the last 61 amino acids of ERα, including residues that form helix 12, abolishes ligand-mediated downregulation of the receptor as do point mutations in the ligand binding domain that impair coactivator binding. In addition, coactivators also are subject to degradation by the 26S proteasome, but their intrinsic transcriptional activity is not affected. These data provide evidence that protein interactions with ERα coactivator binding surfaces are important for ligand-mediated receptor down-regulation and suggest that receptor and coactivator turnover contributes to ERα transcriptional activity.
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UR - http://www.scopus.com/inward/citedby.url?scp=0033638393&partnerID=8YFLogxK
M3 - Article
VL - 5
SP - 939
EP - 948
JO - Molecular Cell
JF - Molecular Cell
SN - 1097-2765
IS - 6
ER -