PXD038141-1

PXD038141 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	A ubiquitin-based effector-to-inhibitor switch coordinates brain, craniofacial, and skin development
Description	The 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.
HostingRepository	MassIVE
AnnounceDate	2023-06-28
AnnouncementXML	Submission_2023-06-28_07:42:58.858.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yan Wang
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationList	Methylthio
Instrument	Orbitrap Fusion Lumos

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2022-11-14 18:59:54	ID requested
⏵ 1	2023-06-28 07:42:59	announced

Publication List

no publication

no publication

Keyword List

submitter keyword: CRL3-KLHL4, GIT1-betaPIX complex, early ectodermal differentiation

submitter keyword: CRL3-KLHL4, GIT1-betaPIX complex, early ectodermal differentiation

Contact List

Yan Wang
contact affiliation	NIH/NIDCR
contact email	wangyan2@nih.gov
lab head
Yan Wang
contact affiliation	University of Maryland College Park
contact email	yanwang@umd.edu
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/MSV000090711/