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Identification of a negative regulatory function for steroid receptors.

Publication ,  Journal Article
McDonnell, DP; Vegeto, E; O'Malley, BW
Published in: Proc Natl Acad Sci U S A
November 15, 1992

This report describes the identification of a negative regulator of estrogen and progesterone receptor function. Using a reconstituted estrogen-responsive transcription system in Saccharomyces cerevisiae, we have identified a "repressor function," which when mutated, increases the transcriptional activity of the estrogen and progesterone receptors. In the case of the estrogen receptor this mutation increases the sensitivity of estrogen-mediated activation by at least four orders of magnitude. Analysis of derivatives of the estrogen receptor indicated that this repressor specifically affects the transcription activity of the TAF1 activation domain of the estrogen receptor. The repressor was cloned by complementation and identified as SSN6, a previously described mediator of glucose repression in yeast. Our results indicate that SSN6 is likely to be involved also in the repression of other cellular activators. Interestingly, deletion of the SSN6 protein allows the antiestrogens ICI 164384 and nafoxidine to behave as more potent agonists of estrogen receptor function, while RU486 also becomes a more potent activator of progesterone receptor function. These data suggest that in wild-type cells the role of hormone is twofold: it promotes DNA binding of the receptor and it also induces a conformational change in the receptor which overcomes the effects of this repressor function.

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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

November 15, 1992

Volume

89

Issue

22

Start / End Page

10563 / 10567

Location

United States

Related Subject Headings

  • beta-Galactosidase
  • Transcription, Genetic
  • Saccharomyces cerevisiae
  • Restriction Mapping
  • Recombinant Proteins
  • Receptors, Progesterone
  • Receptors, Estrogen
  • Promoter Regions, Genetic
  • Polyunsaturated Alkamides
  • Plasmids
 

Citation

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McDonnell, D. P., Vegeto, E., & O’Malley, B. W. (1992). Identification of a negative regulatory function for steroid receptors. Proc Natl Acad Sci U S A, 89(22), 10563–10567. https://doi.org/10.1073/pnas.89.22.10563
McDonnell, D. P., E. Vegeto, and B. W. O’Malley. “Identification of a negative regulatory function for steroid receptors.Proc Natl Acad Sci U S A 89, no. 22 (November 15, 1992): 10563–67. https://doi.org/10.1073/pnas.89.22.10563.
McDonnell DP, Vegeto E, O’Malley BW. Identification of a negative regulatory function for steroid receptors. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10563–7.
McDonnell, D. P., et al. “Identification of a negative regulatory function for steroid receptors.Proc Natl Acad Sci U S A, vol. 89, no. 22, Nov. 1992, pp. 10563–67. Pubmed, doi:10.1073/pnas.89.22.10563.
McDonnell DP, Vegeto E, O’Malley BW. Identification of a negative regulatory function for steroid receptors. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10563–10567.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

November 15, 1992

Volume

89

Issue

22

Start / End Page

10563 / 10567

Location

United States

Related Subject Headings

  • beta-Galactosidase
  • Transcription, Genetic
  • Saccharomyces cerevisiae
  • Restriction Mapping
  • Recombinant Proteins
  • Receptors, Progesterone
  • Receptors, Estrogen
  • Promoter Regions, Genetic
  • Polyunsaturated Alkamides
  • Plasmids