Dynamin II is required for 17?-estradiol signaling and autophagy-based ER? degradation.

ABSTRACT: 17?-estradiol (E2) regulates diverse physiological effects, including cell proliferation, by binding to estrogen receptor ? (ER?). ER? 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 ER? degradation in a typical hormone-dependent feedback loop. Although ER? breakdown proceeds through the 26S proteasome, a role for lysosomes and for some endocytic proteins in controlling ER? degradation has been reported. Here, we studied the role of the endocytic protein dynamin II in E2-dependent ER? signaling and degradation. The results indicate that dynamin II siRNA-mediated knock-down partially prevents E2-induced ER? 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:ER? signaling of physiological functions and uncovers a role for autophagy in the control of ER? turnover.

SUBMITTER: Totta P 

PROVIDER: S-EPMC4806323 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature