| First Author | Shin EM | Year | 2021 |
| Journal | Sci Adv | Volume | 7 |
| Issue | 12 | PubMed ID | 33731348 |
| Mgi Jnum | J:308369 | Mgi Id | MGI:6724615 |
| Doi | 10.1126/sciadv.abe2470 | Citation | Shin EM, et al. (2021) GREB1: An evolutionarily conserved protein with a glycosyltransferase domain links ERalpha glycosylation and stability to cancer. Sci Adv 7(12) |
| abstractText | What covalent modifications control the temporal ubiquitination of ERalpha and hence the duration of its transcriptional activity remain poorly understood. We show that GREB1, an ERalpha-inducible enzyme, catalyzes O-GlcNAcylation of ERalpha at residues T553/S554, which stabilizes ERalpha protein by inhibiting association with the ubiquitin ligase ZNF598. Loss of GREB1-mediated glycosylation of ERalpha results in reduced cellular ERalpha levels and insensitivity to estrogen. Higher GREB1 expression in ERalpha(+ve) breast cancer is associated with greater survival in response to tamoxifen, an ERalpha agonist. Mice lacking Greb1 exhibit growth and fertility defects reminiscent of phenotypes in ERalpha-null mice. In summary, this study identifies GREB1, a protein with an evolutionarily conserved domain related to DNA-modifying glycosyltransferases of bacteriophages and kinetoplastids, as the first inducible and the only other (apart from OGT) O-GlcNAc glycosyltransferase in mammalian cytoplasm and ERalpha as its first substrate. |
