Interaction of 14-3-3 proteins with the estrogen receptor alpha F domain provides a drug target interface.

ABSTRACT: Estrogen receptor alpha (ERα) is involved in numerous physiological and pathological processes, including breast cancer. Breast cancer therapy is therefore currently directed at inhibiting the transcriptional potency of ERα, either by blocking estrogen production through aromatase inhibitors or antiestrogens that compete for hormone binding. Due to resistance, new treatment modalities are needed and as ERα dimerization is essential for its activity, interference with receptor dimerization offers a new opportunity to exploit in drug design. Here we describe a unique mechanism of how ERα dimerization is negatively controlled by interaction with 14-3-3 proteins at the extreme C terminus of the receptor. Moreover, the small-molecule fusicoccin (FC) stabilizes this ERα/14-3-3 interaction. Cocry

SUBMITTER: De Vries-van Leeuwen IJ 

PROVIDER: S-EPMC3670367 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature