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.

Totta, P., Busonero, C., Leone, S., Marino, M., Acconcia, F. (2016). Dynamin II is required for 17β-estradiol signaling and autophagy-based ERα degradation. SCIENTIFIC REPORTS [10.1038/srep23727].

Dynamin II is required for 17β-estradiol signaling and autophagy-based ERα degradation

TOTTA, PIERANGELA;BUSONERO, CLAUDIA;LEONE, STEFANO;MARINO, Maria;ACCONCIA, FILIPPO
2016

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.
Totta, P., Busonero, C., Leone, S., Marino, M., Acconcia, F. (2016). Dynamin II is required for 17β-estradiol signaling and autophagy-based ERα degradation. SCIENTIFIC REPORTS [10.1038/srep23727].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11590/291666
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