PXD053433

PXD053433 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	Inactivation of DET1 causes neurological defects and lethality 1 in mice and humans
Description	COP1 and DET1 are components of an E3 ubiquitin ligase that is conserved from plants to humans. Mammalian COP1 binds to DET1 and is a substrate adaptor for the CUL4A-DDB1-RBX1 RING E3 ligase. Its transcription factor substrates, including c-Jun, ETV4, and ETV5, are targeted for proteasomal degradation to effect rapid transcriptional changes in response to cues such as growth factor deprivation. Here we show that a homozygous DET1R26W mutation that is linked to lethal developmental abnormalities in humans disrupts DET1 binding to DDB1 and compromises E3 ligase function. Human-induced pluripotent stem cells bearing the homozygous DET1R26W mutation expressed ETV4 and ETV5 highly, had alterations in mitochondrial protein expression, and exhibited impaired neuronal differentiation. Mice lacking Det1 died during embryogenesis, while Det1 deletion just in neural stem cells elicited hydrocephalus, cerebellar dysplasia, and neonatal lethality. Our findings highlight an important role for DET1 in the neurological development of mice and humans.
HostingRepository	MassIVE
AnnounceDate	2025-01-24
AnnouncementXML	Submission_2025-01-24_12:07:06.414.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Susan Klaeger
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationList	Oxidation; Carbamidomethyl; Acetyl
Instrument	Orbitrap Eclipse

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-26 08:39:30	ID requested
⏵ 1	2025-01-24 12:07:06	announced

Publication List

no publication

no publication

Keyword List

submitter keyword: DET1, COP1, E3 ubiquitin ligase, neurodevelopment

submitter keyword: DET1, COP1, E3 ubiquitin ligase, neurodevelopment

Contact List

Susan Klaeger
contact affiliation	Genentech, Inc.
contact email	klaeger.susan@gene.com
lab head
Susan Klaeger
contact affiliation	Genentech
contact email	klaeger.susan@gene.com
dataset submitter

Full Dataset Link List

MassIVE dataset URI
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MassIVE dataset URI

Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://massive.ucsd.edu/v08/MSV000095151/