The 26S proteasome is required for estrogen receptor-α and coactivator turnover and for efficient estrogen receptor-α transactivation

David M. Lonard, Zafar Nawaz, Carolyn L. Smith, Bert W. O'Malley

Research output: Contribution to journalArticle

465 Citations (Scopus)

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 languageEnglish
Pages (from-to)939-948
Number of pages10
JournalMolecular Cell
Volume5
Issue number6
StatePublished - Dec 28 2000
Externally publishedYes

Fingerprint

Estrogen Receptors
Transcriptional Activation
Ligands
Down-Regulation
Proteasome Endopeptidase Complex
Ubiquitin
Amino Acid Receptors
Point Mutation
Estradiol
ATP dependent 26S protease
Proteins

ASJC Scopus subject areas

  • Molecular Biology

Cite this

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 journalArticle

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