title: Destabilizing domains derived from the human estrogen receptor.
abstract: Methods to rapidly and reversibly perturb the functions of specific proteins are desirable tools for studies of complex biological processes. We have demonstrated an experimental strategy to regulate the intracellular concentration of any protein of interest by using an engineered destabilizing protein domain and a cell-permeable small molecule. Destabilizing domains have general utility to confer instability to a wide range of proteins including integral transmembrane proteins. This study reports a destabilizing domain system based on the ligand binding domain of the estrogen receptor that can be regulated by one of two synthetic ligands, CMP8 or 4-hydroxytamoxifen.
authors.affiliation: Department of Chemical and Systems Biology, Stanford University, Stanford, California 94305, USA.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Imoto
authors.forename: Ling-chun
authors.initials: LC
authors.lastname: Chen
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Wandless
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites / Q000187:drug effects; D006801:Humans; D008024:Ligands; D008164:Luminescent Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D009154:Mutation; D041681:NIH 3T3 Cells; D015202:Protein Engineering; D011960:Receptors, Estrogen / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology
chemical_list: D001426:Bacterial Proteins; D008024:Ligands; D008164:Luminescent Proteins; D011960:Receptors, Estrogen; C054562:yellow fluorescent protein, Bacteria; D013629:Tamoxifen; C016601:afimoxifene