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Publication : Ubiquitination and deubiquitination of 4E-T regulate neural progenitor cell maintenance and neurogenesis by controlling P-body formation.

First Author  Kedia S Year  2022
Journal  Cell Rep Volume  40
Issue  2 Pages  111070
PubMed ID  35830814 Mgi Jnum  J:326824
Mgi Id  MGI:7316250 Doi  10.1016/j.celrep.2022.111070
Citation  Kedia S, et al. (2022) Ubiquitination and deubiquitination of 4E-T regulate neural progenitor cell maintenance and neurogenesis by controlling P-body formation. Cell Rep 40(2):111070
abstractText  During embryogenesis, neural stem/progenitor cells (NPCs) proliferate and differentiate to form brain tissues. Here, we show that in the developing murine cerebral cortex, the balance between the NPC maintenance and differentiation is coordinated by ubiquitin signals that control the formation of processing bodies (P-bodies), cytoplasmic membraneless organelles critical for cell state regulation. We find that the deubiquitinase Otud4 and the E3 ligase Trim56 counter-regulate the ubiquitination status of a core P-body protein 4E-T to orchestrate the assembly of P-bodies in NPCs. Aberrant induction of 4E-T ubiquitination promotes P-body assembly in NPCs and causes a delay in their cell cycle progression and differentiation. In contrast, loss of 4E-T ubiquitination abrogates P-bodies and results in premature neurogenesis. Thus, our results reveal a critical role of ubiquitin-dependent regulation of P-body formation in NPC maintenance and neurogenesis during brain development.
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