GREB1 : an evolutionarily conserved protein with a glycosyltransferase domain links ERα glycosylation and stability to cancer
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 asso...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2021
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| Online Access: | https://hdl.handle.net/10356/151004 |
| _version_ | 1826110443769298944 |
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| author | 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 |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) 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 |
| author_sort | Shin, Eun Myoung |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T02:34:31Z |
| format | Journal Article |
| id | ntu-10356/151004 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T02:34:31Z |
| publishDate | 2021 |
| record_format | dspace |
| spelling | ntu-10356/1510042023-03-05T16:50:21Z GREB1 : an evolutionarily conserved protein with a glycosyltransferase domain links ERα glycosylation and stability to cancer 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 Lee Kong Chian School of Medicine (LKCMedicine) School of Biological Sciences Institute of Molecular and Cell Biology, A*STAR Science::Medicine Bacteriophages Cytology 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. National Research Foundation (NRF) Published version The V.T. laboratory is funded by the National Research Foundation, Singapore (NRF-CRP17-2017-02). V.T.H. is supported by SINGA program. L.M.I. and L.A. were supported by the Intramural Research Program of the NIH, National Library of Medicine. 2021-06-25T02:35:33Z 2021-06-25T02:35:33Z 2021 Journal Article 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 2375-2548 https://hdl.handle.net/10356/151004 10.1126/sciadv.abe2470 33731348 2-s2.0-85102661172 12 7 eabe2470 en NRF-CRP17-2017-02 Science Advances © 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). application/pdf |
| spellingShingle | Science::Medicine Bacteriophages Cytology 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 GREB1 : an evolutionarily conserved protein with a glycosyltransferase domain links ERα glycosylation and stability to cancer |
| title | GREB1 : an evolutionarily conserved protein with a glycosyltransferase domain links ERα glycosylation and stability to cancer |
| title_full | GREB1 : an evolutionarily conserved protein with a glycosyltransferase domain links ERα glycosylation and stability to cancer |
| title_fullStr | GREB1 : an evolutionarily conserved protein with a glycosyltransferase domain links ERα glycosylation and stability to cancer |
| title_full_unstemmed | GREB1 : an evolutionarily conserved protein with a glycosyltransferase domain links ERα glycosylation and stability to cancer |
| title_short | GREB1 : an evolutionarily conserved protein with a glycosyltransferase domain links ERα glycosylation and stability to cancer |
| title_sort | greb1 an evolutionarily conserved protein with a glycosyltransferase domain links erα glycosylation and stability to cancer |
| topic | Science::Medicine Bacteriophages Cytology |
| url | https://hdl.handle.net/10356/151004 |
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