title: Identification, cloning, and expression of human estrogen receptor-alpha36, a novel variant of human estrogen receptor-alpha66.
abstract: The identification and subsequent cloning of the 66-kDa human estrogen receptor (here termed hER-alpha66), its 46-kDa splice variant hER-alpha46, and the closely related hER-beta have had a profound impact on the generation of new understanding of estrogen-mediated functions and led to progress in diagnosis and treatment of human breast cancer. However, a persistent problem has been that not all findings previously reported in estrogen-stimulated cell proliferation can be explained through the known properties of the different estrogen receptors described. As the consequence of a search for alternative mechanisms to account for these different findings, we have now identified, cloned, and expressed in HEK 293 cells a previously unrecognized 36-kDa variant of hER-alpha66, termed hER-alpha36. hER-alpha36 differs from hER-alpha66 since it lacks both transcriptional activation domains (AF-1 and AF-2) but it retains the DNA-binding domain, and partial dimerization and ligand-binding domains of hER-alpha66. It also contains three myristoylation sites postulated to direct ER-alpha36 to the plasma membrane. It is concluded that ER-alpha36 is a unique variant of ER-alpha66; ER-alpha36 is predicted to function as a dominant-negative effector of hER-alpha66-mediated estrogen-responsive gene pathways and has the potential to trigger membrane-initiated mitogenic estrogen signaling.
authors.affiliation: Cancer Center, Creighton University, Omaha, NE 68178, USA.
authors.forename: Zhaoyi
authors.initials: Z
authors.lastname: Wang
authors.forename: Xintian
authors.initials: X
authors.lastname: Zhang
authors.forename: Peng
authors.initials: P
authors.lastname: Shen
authors.forename: Brian W
authors.initials: BW
authors.lastname: Loggie
authors.forename: Yunchao
authors.initials: Y
authors.lastname: Chang
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Deuel
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D047628:Estrogen Receptor alpha / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D017434:Protein Structure, Tertiary
chemical_list: D047628:Estrogen Receptor alpha; D020033:Protein Isoforms