| First Author | Kouloulia S | Year | 2019 |
| Journal | Cell Rep | Volume | 29 |
| Issue | 11 | Pages | 3620-3635.e7 |
| PubMed ID | 31825840 | Mgi Jnum | J:296924 |
| Mgi Id | MGI:6468836 | Doi | 10.1016/j.celrep.2019.11.023 |
| Citation | Kouloulia S, et al. (2019) Raptor-Mediated Proteasomal Degradation of Deamidated 4E-BP2 Regulates Postnatal Neuronal Translation and NF-kappaB Activity. Cell Rep 29(11):3620-3635.e7 |
| abstractText | The translation initiation repressor 4E-BP2 is deamidated in the brain on asparagines N99/N102 during early postnatal brain development. This post-translational modification enhances 4E-BP2 association with Raptor, a central component of mTORC1 and alters the kinetics of excitatory synaptic transmission. We show that 4E-BP2 deamidation is neuron specific, occurs in the human brain, and changes 4E-BP2 subcellular localization, but not its disordered structure state. We demonstrate that deamidated 4E-BP2 is ubiquitinated more and degrades faster than the unmodified protein. We find that enhanced deamidated 4E-BP2 degradation is dependent on Raptor binding, concomitant with increased association with a Raptor-CUL4B E3 ubiquitin ligase complex. Deamidated 4E-BP2 stability is promoted by inhibiting mTORC1 or glutamate receptors. We further demonstrate that deamidated 4E-BP2 regulates the translation of a distinct pool of mRNAs linked to cerebral development, mitochondria, and NF-kappaB activity, and thus may be crucial for postnatal brain development in neurodevelopmental disorders, such as ASD. |
