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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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
The Royal Society
2025-01-01
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| Series: | Open Biology |
| Subjects: | |
| Online Access: | https://royalsocietypublishing.org/doi/10.1098/rsob.250064 |
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| Summary: | 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. |
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| ISSN: | 2046-2441 |