Membrane association of estrogen receptor α and β influences 17β-estradiol-mediated cancer cell proliferation

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 (ERα and ERβ) belonging to the nuclear receptor superfamily have been added to the palmitoylproteoma. S-Palmitoylation allows ERα and ERβ localization at the plasma membrane, where they associate with caveolin-1. Upon 17β-estradiol (E2) stimulation, ERα dissociates from caveolin-1 allowing the activation of rapid signals relevant for cell proliferation. In contrast to ERα, E2 increases ERβ 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 ERα and ERβ localization at the plasma membrane and the regulation of different E2-induced non-genomic functions relevant for controlling cell proliferation.