dc.contributor.author | Kouloulia, Stella | en_US |
dc.contributor.author | Hallin, Erik Ingmar | en_US |
dc.contributor.author | Simbriger, Konstanze | en_US |
dc.contributor.author | Amorim, Ines S | en_US |
dc.contributor.author | Lach, Gilliard | en_US |
dc.contributor.author | Amvrosiadis, Theoklitos | en_US |
dc.contributor.author | Chalkiadaki, Kleanthi | en_US |
dc.contributor.author | Kampaite, Agniete | en_US |
dc.contributor.author | Truong, Vinh Tai | en_US |
dc.contributor.author | Hooshmandi, Mehdi | en_US |
dc.contributor.author | Jafarnejad, Seyed Mehdi | en_US |
dc.contributor.author | Skehel, Paul | en_US |
dc.contributor.author | Kursula, Petri | en_US |
dc.contributor.author | Khoutorsky, Arkady | en_US |
dc.contributor.author | Gkogkas, Christos | en_US |
dc.date.accessioned | 2020-08-05T12:58:12Z | |
dc.date.available | 2020-08-05T12:58:12Z | |
dc.date.issued | 2019 | |
dc.Published | Kouloulia, Hallin EI, Simbriger, Amorim, Lach, Amvrosiadis, Chalkiadaki, Kampaite, Truong, Hooshmandi, Jafarnejad, Skehel, Kursula P, Khoutorsky, Gkogkas C. Raptor-Mediated Proteasomal Degradation of Deamidated 4E-BP2 Regulates Postnatal Neuronal Translation and NF-κB Activity. Cell reports. 2019;29(11):3620-3635 | eng |
dc.identifier.issn | 2211-1247 | |
dc.identifier.uri | https://hdl.handle.net/1956/23473 | |
dc.description.abstract | 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-κB activity, and thus may be crucial for postnatal brain development in neurodevelopmental disorders, such as ASD. | en_US |
dc.language.iso | eng | eng |
dc.publisher | Elsevier | eng |
dc.relation.uri | https://www.sciencedirect.com/science/article/pii/S2211124719314949 | |
dc.rights | Attribution CC BY | eng |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | eng |
dc.title | Raptor-Mediated Proteasomal Degradation of Deamidated 4E-BP2 Regulates Postnatal Neuronal Translation and NF-κB Activity | en_US |
dc.type | Peer reviewed | |
dc.type | Journal article | |
dc.date.updated | 2020-02-03T09:55:31Z | |
dc.description.version | publishedVersion | en_US |
dc.rights.holder | Copyright 2019 The Author(s) | |
dc.identifier.doi | https://doi.org/10.1016/j.celrep.2019.11.023 | |
dc.identifier.cristin | 1779128 | |
dc.source.journal | Cell reports | |
dc.relation.project | Norges forskningsråd: 226244/F50 | |