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pubmed:abstractText |
Protein monoubiquitination (monoUbq) (i.e., the attachment of one single ubiquitin to the substrate) is a non-proteolytic reversible modification that controls protein functions. Among other proteins, the estrogen receptor ? (ER?), which mediates the pleiotropic effects of the cognate hormone 17?-estradiol (E2), is a monoubiquitinated protein. Although it has been demonstrated that E2 rapidly reduces ER? monoUbq in breast cancer cells, the impact of monoUbq in the regulation of the ER? activities is poorly appreciated. Here, we show that mutation of the ER? monoUbq sites prevents the E2-induced ER? phosphorylation in the serine residue 118 (S118), reduces ER? transcriptional activity, and precludes the ER?-mediated extranuclear activation of signaling pathways (i.e., AKT activation) thus impeding the E2-induced cyclin D1 promoter activation and consequently cell proliferation. In addition, the interference with ER? monoUbq deregulates E2-induced association of ER? to the insulin like growth factor receptor (IGF-1-R). Altogether these data demonstrate an inherent role for monoUbq in ER? signaling and point to the physiological function of ER? monoUbq in the regulation of E2-induced cell proliferation.
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