O-GlcNAcylation of the intellectual disability protein DDX3X exerts proteostatic cell cycle control
O-GlcNAcylation of intracellular proteins is a key regulator of diverse cellular and developmental processes. Previous studies have demonstrated the acute sensitivity of cell cycle progression to chemical and genetic manipulation of O-GlcNAc homeostasis. However, the mechanisms by which O-GlcNAc reg...
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| Language: | English |
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The Royal Society
2025-01-01
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| Series: | Open Biology |
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| Online Access: | https://royalsocietypublishing.org/doi/10.1098/rsob.250064 |
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| author | Conor W. Mitchell Huijie Yuan Marie Sønderstrup-Jensen Andrew T. Ferenbach Daan M. F. van Aalten |
| author_facet | Conor W. Mitchell Huijie Yuan Marie Sønderstrup-Jensen Andrew T. Ferenbach Daan M. F. van Aalten |
| author_sort | Conor W. Mitchell |
| collection | DOAJ |
| description | O-GlcNAcylation of intracellular proteins is a key regulator of diverse cellular and developmental processes. Previous studies have demonstrated the acute sensitivity of cell cycle progression to chemical and genetic manipulation of O-GlcNAc homeostasis. However, the mechanisms by which O-GlcNAc regulates the cell cycle remain poorly understood. Here, we report Ser584 O-GlcNAcylation of the RNA helicase DDX3X, a microcephaly associated protein, as a proteostatic mechanism regulating S-phase entry. Loss of Ser584 O-GlcNAcylation promoted degradation of DDX3X by the proteasome, resulting in reduced expression of the DDX3X target gene cyclin E1 and impaired cell cycle progression from G1 to S phase. These findings display how a single O-GlcNAc site affects DDX3X stability and thereby the cell cycle. |
| format | Article |
| id | doaj-art-a868cb0a0d274d69988b1374eddcfd17 |
| institution | DOAJ |
| issn | 2046-2441 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | The Royal Society |
| record_format | Article |
| series | Open Biology |
| spelling | doaj-art-a868cb0a0d274d69988b1374eddcfd172025-08-20T02:44:39ZengThe Royal SocietyOpen Biology2046-24412025-01-0115710.1098/rsob.250064O-GlcNAcylation of the intellectual disability protein DDX3X exerts proteostatic cell cycle controlConor W. Mitchell0Huijie Yuan1Marie Sønderstrup-Jensen2Andrew T. Ferenbach3Daan M. F. van Aalten4Department of Molecular Biology and Genetics, Aarhus Universitet, Aarhus, DenmarkDepartment of Molecular Biology and Genetics, Aarhus Universitet, Aarhus, DenmarkDepartment of Molecular Biology and Genetics, Aarhus Universitet, Aarhus, DenmarkDepartment of Molecular Biology and Genetics, Aarhus Universitet, Aarhus, DenmarkDepartment of Molecular Biology and Genetics, Aarhus Universitet, Aarhus, DenmarkO-GlcNAcylation of intracellular proteins is a key regulator of diverse cellular and developmental processes. Previous studies have demonstrated the acute sensitivity of cell cycle progression to chemical and genetic manipulation of O-GlcNAc homeostasis. However, the mechanisms by which O-GlcNAc regulates the cell cycle remain poorly understood. Here, we report Ser584 O-GlcNAcylation of the RNA helicase DDX3X, a microcephaly associated protein, as a proteostatic mechanism regulating S-phase entry. Loss of Ser584 O-GlcNAcylation promoted degradation of DDX3X by the proteasome, resulting in reduced expression of the DDX3X target gene cyclin E1 and impaired cell cycle progression from G1 to S phase. These findings display how a single O-GlcNAc site affects DDX3X stability and thereby the cell cycle.https://royalsocietypublishing.org/doi/10.1098/rsob.250064O-GlcNAccell cyclecell signalling |
| spellingShingle | Conor W. Mitchell Huijie Yuan Marie Sønderstrup-Jensen Andrew T. Ferenbach Daan M. F. van Aalten O-GlcNAcylation of the intellectual disability protein DDX3X exerts proteostatic cell cycle control Open Biology O-GlcNAc cell cycle cell signalling |
| title | O-GlcNAcylation of the intellectual disability protein DDX3X exerts proteostatic cell cycle control |
| title_full | O-GlcNAcylation of the intellectual disability protein DDX3X exerts proteostatic cell cycle control |
| title_fullStr | O-GlcNAcylation of the intellectual disability protein DDX3X exerts proteostatic cell cycle control |
| title_full_unstemmed | O-GlcNAcylation of the intellectual disability protein DDX3X exerts proteostatic cell cycle control |
| title_short | O-GlcNAcylation of the intellectual disability protein DDX3X exerts proteostatic cell cycle control |
| title_sort | o glcnacylation of the intellectual disability protein ddx3x exerts proteostatic cell cycle control |
| topic | O-GlcNAc cell cycle cell signalling |
| url | https://royalsocietypublishing.org/doi/10.1098/rsob.250064 |
| work_keys_str_mv | AT conorwmitchell oglcnacylationoftheintellectualdisabilityproteinddx3xexertsproteostaticcellcyclecontrol AT huijieyuan oglcnacylationoftheintellectualdisabilityproteinddx3xexertsproteostaticcellcyclecontrol AT mariesønderstrupjensen oglcnacylationoftheintellectualdisabilityproteinddx3xexertsproteostaticcellcyclecontrol AT andrewtferenbach oglcnacylationoftheintellectualdisabilityproteinddx3xexertsproteostaticcellcyclecontrol AT daanmfvanaalten oglcnacylationoftheintellectualdisabilityproteinddx3xexertsproteostaticcellcyclecontrol |