FLP recombinase/estrogen receptor fusion proteins require the receptor D domain for responsiveness to antagonists, but not agonists

Molecular Endocrinology
M NicholsA Francis Stewart

Abstract

The ligand-binding domains of steroid receptors convey ligand-dependent regulation to certain proteins to which they are fused. Here we characterize fusion proteins between a site-specific recombinase, FLP, and steroid receptor ligand-binding domains. These proteins convert ligand binding into DNA recombination. Thus, ligand binding is directly coupled to an enzyme activity that is easily measured by DNA rearrangements or heritable genetic changes in marker gene expression, as opposed to the multiple events leading to transcription. Recombination by a FLP-estrogen receptor (FLP-EBD) fusion is activated by all tested estrogens, whether agonists or antagonists, indicating that all induce EBD release from the 90-kDa heat shock protein complex. Altering the distance between FLP and the EBD domain in the fusion proteins, by reducing the included length of the estrogen receptor D domain, affects ligand efficacy. A FLP-EBD with no D domain shows reduced inducibility by agonists and, unexpectedly, complete insensitivity to induction by all antagonists tested. A FLP-EBD including some D domain shows a ligand-inducible phenotype intermediate to those displayed by FLP-EBDs containing all or none of the D domain. Thus, we observed a tether...Continue Reading

Citations

Jan 31, 2002·Proceedings of the National Academy of Sciences of the United States of America·Akiko KoideShohei Koide
Apr 29, 1998·Nucleic Acids Research·F SchwenkA F Stewart
Jan 11, 2000·Nucleic Acids Research·T H ChengM R Gartenberg
May 15, 2002·Breast Cancer Research and Treatment·Mark Nichols, Kenneth S McCarty
Jan 18, 2018·Chembiochem : a European Journal of Chemical Biology·Weiting ZhangDavid Bensimon

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