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PXD035852-1

PXD035852 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleFine-tuning of mTOR signaling by the UBE4B-KLHL22 E3 ubiquitin ligase cascade in brain development
DescriptionAbstract Spatiotemporal regulation of the mechanistic target of rapamycin (mTOR) pathway is pivotal for establishment of brain architecture. Dysregulation of mTOR signaling is associated with a variety of neurodevelopmental disorders (NDDs). Here, we discover that the UBE4B-KLHL22 E3 ubiquitin ligase cascade regulates mTOR activity in neurodevelopment. In a mouse model with UBE4B conditionally deleted in the nervous system, animals display severe growth defects, spontaneous seizures, and premature death. Loss of UBE4B in the brains of mutant mice results in depletion of neural precursor cells (NPCs), impairment of neurogenesis, and enlargement of neuronal soma. Mechanistically, UBE4B polyubiquitinates and degrades KLHL22, an E3 ligase previously shown to degrade the GATOR1 component DEPDC5. Deletion of UBE4B causes upregulation of KLHL22 and hyperactivation of mTOR, leading to defective proliferation and differentiation of NPCs. Suppression of KLHL22 expression reverses the elevated activity of mTOR caused by acute local deletion of UBE4B in the dentate gyrus (DG). Prenatal treatment with the mTOR inhibitor rapamycin rescues neurogenesis defects in Ube4b mutant mice. Taken together, these findings demonstrate that UBE4B and KLHL22 are essential for maintenance and differentiation of the precursor pool through fine-tuning of mTOR activity.
HostingRepositoryPRIDE
AnnounceDate2022-12-12
AnnouncementXMLSubmission_2022-12-12_05:59:57.396.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterXinShu
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListacetylated residue; monohydroxylated residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-08-07 03:42:15ID requested
12022-12-12 05:59:57announced
22023-11-14 08:57:15announced2023-11-14: Updated project metadata.
Publication List
Keyword List
submitter keyword: Mouse brain,MS,UBE4B
Contact List
Xiang_XingKong
contact affiliationZJU
contact email11718017@zju.edu.cn
lab head
XinShu
contact affiliationZhejiang university
contact emailsx725@zju.edu.cn
dataset submitter
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Dataset FTP location
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