title: Membrane association of estrogen receptor alpha and beta influences 17beta-estradiol-mediated cancer cell proliferation.
abstract: S-Palmitoylation is a widespread post-translational modification of integral and/or peripheral proteins occurring in all eukaryotic cells. The family of S-palmitoylated proteins is large and diverse and recently, estrogen receptor isoforms (ERalpha and ERbeta) belonging to the nuclear receptor superfamily have been added to the palmitoylproteoma. S-Palmitoylation allows ERalpha and ERbeta localization at the plasma membrane, where they associate with caveolin-1. Upon 17beta-estradiol (E2) stimulation, ERalpha dissociates from caveolin-1 allowing the activation of rapid signals relevant for cell proliferation. In contrast to ERalpha, E2 increases ERbeta association with caveolin-1 and activates p38 kinase and the downstream pro-apoptotic cascade (i.e., caspase-3 activation and PARP cleavage). These data highlight the physiological role of palmitoylation in modulating the ERalpha and ERbeta localization at the plasma membrane and the regulation of different E2-induced non-genomic functions relevant for controlling cell proliferation.
authors.affiliation: Department of Biology, University Roma Tre, Viale G. Marconi 446, I-00146 Roma, Italy. m.marino@uniroma3.it
authors.forename: Maria
authors.initials: M
authors.lastname: Marino
authors.forename: Paolo
authors.initials: P
authors.lastname: Ascenzi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051242:Caveolin 1 / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D004958:Estradiol / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D006801:Humans; D054878:Lipoylation; D008954:Models, Biological; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D051242:Caveolin 1; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004958:Estradiol; D048051:p38 Mitogen-Activated Protein Kinases