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|Title:||GREB1 : an evolutionarily conserved protein with a glycosyltransferase domain links ERα glycosylation and stability to cancer||Authors:||Shin, Eun Myoung
Huynh, Vinh Thang
Neja, Sultan Abda
Liu, Chia Yi
Tan, Nguan Soon
Iyer, Lakshminarayan M.
|Keywords:||Science::Medicine||Issue Date:||2021||Source:||Shin, E. M., Huynh, V. T., Neja, S. A., Liu, C. Y., Raju, A., Tan, K., Tan, N. S., Gunaratne, J., Bi, X., Iyer, L. M., Aravind, L. & Tergaonkar, V. (2021). GREB1 : an evolutionarily conserved protein with a glycosyltransferase domain links ERα glycosylation and stability to cancer. Science Advances, 7(12), eabe2470-. https://dx.doi.org/10.1126/sciadv.abe2470||Project:||NRF-CRP17-2017-02||Journal:||Science Advances||Abstract:||What covalent modifications control the temporal ubiquitination of ERα and hence the duration of its transcriptional activity remain poorly understood. We show that GREB1, an ERα-inducible enzyme, catalyzes O-GlcNAcylation of ERα at residues T553/S554, which stabilizes ERα protein by inhibiting association with the ubiquitin ligase ZNF598. Loss of GREB1-mediated glycosylation of ERα results in reduced cellular ERα levels and insensitivity to estrogen. Higher GREB1 expression in ERα+ve breast cancer is associated with greater survival in response to tamoxifen, an ERα agonist. Mice lacking Greb1 exhibit growth and fertility defects reminiscent of phenotypes in ERα-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 ERα as its first substrate.||URI:||https://hdl.handle.net/10356/151004||ISSN:||2375-2548||DOI:||10.1126/sciadv.abe2470||Rights:||© 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).||Fulltext Permission:||open||Fulltext Availability:||With Fulltext|
|Appears in Collections:||LKCMedicine Journal Articles|
Updated on Nov 30, 2021
Updated on Nov 30, 2021
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