Identification of a third autonomous activation domain within the human estrogen receptor.

Journal Article

Using a genetic selection system established in the yeast Saccharomyces cerevisiae, we have isolated, by random mutagenesis of the human estrogen receptor (ER), six mutants that display constitutive transcriptional activity. All of the mutants identified contained single base insertions or deletions leading to frameshift mutations, resulting in receptor truncations within the hormone-binding domain between amino acids (aa) 324-351. Interestingly, an ER mutant (aa 1-282) was transcriptionally inactive in yeast, suggesting that a domain important for transcriptional activity lies between aa 282 and 351 within human ER. Deletions representative of the mutants isolated in the yeast system were created in mammalian expression vectors and examined for transcriptional activity in animal cells to determine the physiological relevance of this domain. Receptors truncated at aa 282 were either weakly active or inactive; however, an ER deletion at aa 351 was approximately 50% as active as wild type ER (induced with estrogen). Furthermore, a chimeric receptor consisting of the DNA binding domain of GAL4 fused to aa 282-351 of the human ER was transcriptionally active on a GAL4 reporter. We conclude, therefore, that an autonomous activation domain (referred to as AF2a), functional in both yeast and mammalian cells, lies between aa 282-351 of the human ER.

Full Text

Duke Authors

Cited Authors

  • Norris, JD; Fan, D; Kerner, SA; McDonnell, DP

Published Date

  • June 1997

Published In

Volume / Issue

  • 11 / 6

Start / End Page

  • 747 - 754

PubMed ID

  • 9171238

International Standard Serial Number (ISSN)

  • 0888-8809

Digital Object Identifier (DOI)

  • 10.1210/mend.11.6.0008

Language

  • eng

Conference Location

  • United States