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PXD038141-1

PXD038141 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleA ubiquitin-based effector-to-inhibitor switch coordinates brain, craniofacial, and skin development
DescriptionThe molecular mechanisms that coordinate patterning of the embryonic ectoderm into spatially distinct lineages to form the nervous system, epidermis, and craniofacial structures are unclear. Here, biochemical disease-variant profiling reveals a posttranslational pathway that drives early ectodermal differentiation in the vertebrate head. The anteriorly expressed ubiquitin ligase CRL3-KLHL4 restricts signaling of the ubiquitous cytoskeletal regulator CDC42. This regulation relies on the CDC42-activating complex GIT1-betaPIX, which CRL3-KLHL4 exploits as a substrate-specific co-adaptor to recognize and monoubiquitylate PAK1. Surprisingly, we find that ubiquitylation converts the canonical CDC42 effector PAK1 into a CDC42 inhibitor. Loss of CRL3-KLHL4 or a disease-associated KLHL4 variant reduce PAK1 ubiquitylation causing overactivation of CDC42 signaling and defective ectodermal patterning and neurulation. Thus, tissue-specific restriction of CDC42 signaling by a ubiquitin-based effector-to-inhibitor is essential for face, brain, and skin formation, revealing how cell-fate and morphometric changes are coordinated to ensure faithful organ development.
HostingRepositoryMassIVE
AnnounceDate2023-06-28
AnnouncementXMLSubmission_2023-06-28_07:42:58.858.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterYan Wang
SpeciesList scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationListMethylthio
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-11-14 18:59:54ID requested
12023-06-28 07:42:59announced
Publication List
no publication
Keyword List
submitter keyword: CRL3-KLHL4, GIT1-betaPIX complex, early ectodermal differentiation
Contact List
Yan Wang
contact affiliationNIH/NIDCR
contact emailwangyan2@nih.gov
lab head
Yan Wang
contact affiliationUniversity of Maryland College Park
contact emailyanwang@umd.edu
dataset submitter
Full Dataset Link List
MassIVE dataset URI
Dataset FTP location
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