title: Dynamin II is required for 17β-estradiol signaling and autophagy-based ERα degradation.
abstract: 17β-estradiol (E2) regulates diverse physiological effects, including cell proliferation, by binding to estrogen receptor α (ERα). ERα is both a transcription factor that drives E2-sensitive gene expression and an extra-nuclear localized receptor that triggers the activation of diverse kinase cascades. While E2 triggers cell proliferation, it also induces ERα degradation in a typical hormone-dependent feedback loop. Although ERα breakdown proceeds through the 26S proteasome, a role for lysosomes and for some endocytic proteins in controlling ERα degradation has been reported. Here, we studied the role of the endocytic protein dynamin II in E2-dependent ERα signaling and degradation. The results indicate that dynamin II siRNA-mediated knock-down partially prevents E2-induced ERα degradation through the inhibition of an autophagy-based pathway and impairs E2-induced cell proliferation signaling. Altogether, these data demonstrate that dynamin II is required for the E2:ERα signaling of physiological functions and uncovers a role for autophagy in the control of ERα turnover.
authors.affiliation: Department of Sciences, Section Biomedical Sciences and Technology, University Roma Tre, Viale Guglielmo Marconi, 446, I-00146, Rome, Italy.
authors.forename: Pierangela
authors.initials: P
authors.lastname: Totta
authors.affiliation: Department of Sciences, Section Biomedical Sciences and Technology, University Roma Tre, Viale Guglielmo Marconi, 446, I-00146, Rome, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Busonero
authors.affiliation: Department of Sciences, Section Biomedical Sciences and Technology, University Roma Tre, Viale Guglielmo Marconi, 446, I-00146, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Leone
authors.affiliation: Department of Sciences, Section Biomedical Sciences and Technology, University Roma Tre, Viale Guglielmo Marconi, 446, I-00146, Rome, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Marino
authors.affiliation: Department of Sciences, Section Biomedical Sciences and Technology, University Roma Tre, Viale Guglielmo Marconi, 446, I-00146, Rome, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Acconcia
mesh_terms: D000071182:Autophagosomes / Q000378:metabolism; D001343:Autophagy; D002460:Cell Line; D049109:Cell Proliferation; D034285:Dynamin II; D034281:Dynamins / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D015398:Signal Transduction
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D004958:Estradiol; C000593490:DNM2 protein, human; D034285:Dynamin II; D034281:Dynamins