""The sex hormone 17-estradiol (E2) exerts its pleiotropic effects through the binding to the ligand-activated transcription factor estrogen receptor alpha (ERThe E2:ER complex regulates several physiological processes including cell survival and proliferation through transcriptional [i.e., estrogen responsive element (ERE)-based gene transcription] and non-transcriptional membrane-initiated effects (i.e., activation of signalling cascades).. Many post-translational modifications occur on ER and are regulated by E2. Indeed, E2 induces ER phosphorylation that facilitates ER-dependent gene transcription while the hormone reduces ER palmitoylation, thus modulating the amount of the receptor located at the plasma membrane and the E2 signalling to cell proliferation. The ER is also an ubiquitinated protein: ER polyubiquitination (polyUbq) increases upon E2 binding and E2-dependent ER degradation occurs in parallel to the appearance of the E2-evoked physiological effects.. However, the role of ER post-translational modifications in the regulation of the E2-dependent cell proliferation is poorly appreciated. Therefore, we analyzed here how ER phosphorylation, palmitoylation and ubiquitination influence E2-induced cell proliferation in an integrated manner.. Our results demonstrate that the polyUbq-based ER degradation cross-talks with receptor phosphorylation and palmitoylation and is required for the E2-dependent control of cell proliferation. Furthermore, the lack of ER palmitoylation fastens E2-induced polyUbq-dependent ER degradation and prevents both receptor phosphorylation and E2-dependent cell proliferation. Therefore, these data demonstrate that a code of diverse post-translational modifications occurs on ER and uncover a new model of E2:ER cellular signalling in which the E2-dependent control of ER post-translational modifications finely coordinates the E2 ability to regulate cell proliferation.. ""
Acconcia, F., Pesiri, V., La Rosa, P., Pallottini, V., Marino, M. (2012). Diverse post-translational modifications of estrogen receptor α cross-talk in the coordination of 17 β-estradiol-dependent cell proliferation. In Abstract of the 63rd National Congress of the Italian Physiological Society 21-23 September 2012, Verona, Italy.
Diverse post-translational modifications of estrogen receptor α cross-talk in the coordination of 17 β-estradiol-dependent cell proliferation
ACCONCIA, FILIPPO;PESIRI, VALERIA;PALLOTTINI, Valentina;MARINO, Maria
2012-01-01
Abstract
""The sex hormone 17-estradiol (E2) exerts its pleiotropic effects through the binding to the ligand-activated transcription factor estrogen receptor alpha (ERThe E2:ER complex regulates several physiological processes including cell survival and proliferation through transcriptional [i.e., estrogen responsive element (ERE)-based gene transcription] and non-transcriptional membrane-initiated effects (i.e., activation of signalling cascades).. Many post-translational modifications occur on ER and are regulated by E2. Indeed, E2 induces ER phosphorylation that facilitates ER-dependent gene transcription while the hormone reduces ER palmitoylation, thus modulating the amount of the receptor located at the plasma membrane and the E2 signalling to cell proliferation. The ER is also an ubiquitinated protein: ER polyubiquitination (polyUbq) increases upon E2 binding and E2-dependent ER degradation occurs in parallel to the appearance of the E2-evoked physiological effects.. However, the role of ER post-translational modifications in the regulation of the E2-dependent cell proliferation is poorly appreciated. Therefore, we analyzed here how ER phosphorylation, palmitoylation and ubiquitination influence E2-induced cell proliferation in an integrated manner.. Our results demonstrate that the polyUbq-based ER degradation cross-talks with receptor phosphorylation and palmitoylation and is required for the E2-dependent control of cell proliferation. Furthermore, the lack of ER palmitoylation fastens E2-induced polyUbq-dependent ER degradation and prevents both receptor phosphorylation and E2-dependent cell proliferation. Therefore, these data demonstrate that a code of diverse post-translational modifications occurs on ER and uncover a new model of E2:ER cellular signalling in which the E2-dependent control of ER post-translational modifications finely coordinates the E2 ability to regulate cell proliferation.. ""I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.