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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
Raju, Anandhkumar
Tan, Kelly
Tan, Nguan Soon
Gunaratne, Jayantha
Bi, Xuezhi
Iyer, Lakshminarayan M.
Aravind, L.
Tergaonkar, Vinay
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-.
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.
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

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