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Coactivator AIB1 links estrogen receptor transcriptional activity and stability.

Publication ,  Journal Article
Shao, W; Keeton, EK; McDonnell, DP; Brown, M
Published in: Proc Natl Acad Sci U S A
August 10, 2004

Agonist-mediated degradation of estrogen receptor alpha (ERalpha) has been associated with its transcriptional activity. However, the mechanism by which ERalpha is targeted for degradation and whether there is a direct functional link between ERalpha stability and ERalpha-mediated transactivation have not been elucidated. Here we provide evidence that the p160 coactivator, AIB1, uniquely mediates agonist-induced, but not antagonist-induced, ERalpha degradation. We show that AIB1 recruitment by ERalpha is not only necessary but also sufficient to promote degradation. Suppression of AIB1 levels leads to ERalpha stabilization in the presence of 17beta-estradiol and, despite increased ERalpha levels, reduced recruitment of ERalpha to endogenous target gene promoters. In addition, association of RNA polymerase II with ERalpha target promoters is lost when AIB1 is suppressed, leading to inhibition of target gene transcription. AIB1 thus plays a dual role in regulating ERalpha activity, one in recruiting transcription factors including other coactivators involved in gene activation and the other in regulating ERalpha protein degradation mediated by the ubiquitin-proteosome machinery.

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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

August 10, 2004

Volume

101

Issue

32

Start / End Page

11599 / 11604

Location

United States

Related Subject Headings

  • Transcriptional Activation
  • Transcription Factors
  • Receptors, Estrogen
  • RNA Polymerase II
  • Protein Binding
  • Promoter Regions, Genetic
  • Nuclear Receptor Coactivator 3
  • Humans
  • Estrogens
  • Estrogen Receptor alpha
 

Citation

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Shao, W., Keeton, E. K., McDonnell, D. P., & Brown, M. (2004). Coactivator AIB1 links estrogen receptor transcriptional activity and stability. Proc Natl Acad Sci U S A, 101(32), 11599–11604. https://doi.org/10.1073/pnas.0402997101
Shao, Wenlin, Erika Krasnickas Keeton, Donald P. McDonnell, and Myles Brown. “Coactivator AIB1 links estrogen receptor transcriptional activity and stability.Proc Natl Acad Sci U S A 101, no. 32 (August 10, 2004): 11599–604. https://doi.org/10.1073/pnas.0402997101.
Shao W, Keeton EK, McDonnell DP, Brown M. Coactivator AIB1 links estrogen receptor transcriptional activity and stability. Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11599–604.
Shao, Wenlin, et al. “Coactivator AIB1 links estrogen receptor transcriptional activity and stability.Proc Natl Acad Sci U S A, vol. 101, no. 32, Aug. 2004, pp. 11599–604. Pubmed, doi:10.1073/pnas.0402997101.
Shao W, Keeton EK, McDonnell DP, Brown M. Coactivator AIB1 links estrogen receptor transcriptional activity and stability. Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11599–11604.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

August 10, 2004

Volume

101

Issue

32

Start / End Page

11599 / 11604

Location

United States

Related Subject Headings

  • Transcriptional Activation
  • Transcription Factors
  • Receptors, Estrogen
  • RNA Polymerase II
  • Protein Binding
  • Promoter Regions, Genetic
  • Nuclear Receptor Coactivator 3
  • Humans
  • Estrogens
  • Estrogen Receptor alpha