The estrogen receptor (ER) is a member of the nuclear receptor family of ligand-activated transcription factors, and is a target for numerous endocrine disrupting xenobiotics in the environment. Many of these compounds (xenoestrogens) are known to elicit effects by binding to and activating, inactivating, or selectively activating estrogen receptor. However, little is currently known about the molecular-level processes which follow binding of xenoestrogen to receptor. We are studying the xenoligand-dependent assembly of protein complexes around the ER using a variety of functional proteomics approaches. These include in vivo methods of complex assembly around recombinant, affinity-tagged ER in human cell lines, followed by mass spectrometric analysis of the isolated complexes as well as in vitro analysis of protein complex assembly in real-time using surface plasmon resonance spectroscopy (SPR) coupled to mass spectrometry. The overall goal of this work is to gain insight into the differences in molecular mechanisms of endocrine disruption initiated by diverse, environmentally-relevant xenoestrogens.
Mechanisms of Xenoestrogen Stress: A Proteomic and Functional Genomic Approach
P. Lee Ferguson (PI), Tara Sabo-Attwood (PI)
National Institute of Health (NIH/NIEHS)