Using Genetic Means to Identify Factors that Affect Estrogen Receptor Function
Abstract
The mechanism of signal transduction by the estrogen receptor (ER) is complex and not fully understood. In the absence of estradiol, ER, like other steroid receptors, is complexed with Hsp9O and other molecular chaperone components, including an immunophilin, and p23. This Hsp9O-based chaperone complex is thought to repress ER's transcriptional regulatory activities while maintaining the receptor in a conformation that is competent for high affinity steroid binding. However, a role for p23 in ER signal transduction has not been demonstrated. Using a mutant ER (G4OOV) with decreased hormone binding capacity as a substrate in a dosage suppression screen in yeast (S. cerevisiae), we identified the yeast homologue of the human p23 protein (yhp23) as a positive regulator of ER function. Overexpression of yhp23 in yeast increases ER transcriptional activation by increasing estradiol binding in vivo. Using a yhp23-GFP fusion protein, we further demonstrate that yhp23 colocalizes with ER within the nuclei of yeast, and that this colocalization is reversed by estradiol treatment. Finally, ectopic expression of human p23 in MCF-7 breast cancer cells increases transcriptional activation by endogenous ER. Together, these results strongly suggest that p23 plays an important role in ER signal transduction.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1999
- Accession Number
- ADA385428
Entities
People
- Roland Knoblauch
Organizations
- NYU Langone Health