Transactivation Function-1-Mediated Partial Agonist Activity of Selective Estrogen Receptor Modulator Requires Homo-Dimerization of the Estrogen Receptor ? Ligand Binding Domain.

ABSTRACT: The isolation of estrogen receptor alpha (ER?) cDNA was successful around 30 years ago. The characteristics of ER? protein have been examined from various aspects, primarily through in vitro cell culture studies, but more recently using in vivo experimental models. There remains, however, some uncharacterized ER? functionalities. In particular, the mechanism of partial agonist activity of selective estrogen receptor modulators (SERMs) that involves control of the N-terminal transcription function of ER?, termed AF-1, is still an unsolved ER? functionality. We review the possible mechanism of SERM-dependent regulation of ER? AF-1-mediated transcriptional activity, which includes the role of helix 12 of ER? ligand binding domain (LBD) for SERM-dependent AF-1 regulation. In addition, we describe a specific portion of the LBD that associates with blocking AF-1 activity with an additional role of the F-domain in mediating SERM activity.

SUBMITTER: Arao Y 

PROVIDER: S-EPMC6695978 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature