PXD048554-1

PXD048554 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	The N-acetylglucosaminyltransferase Radical Fringe contributes to defects in JAG1-dependent turnover and signaling of NOTCH3 CADASIL mutants
Description	Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic vascular dementia characterized by age-related degeneration of vascular mural cells and accumulation of a NOTCH3 mutant protein. NOTCH3 functions as a signaling receptor, activating downstream gene expression in response to ligands like JAG1 and DLL4, which regulate the development and survival of mural cells. This signal transduction process is thought to be connected with NOTCH3 endocytic degradation. However, the specific cellular circumstances that modulate turnover and signaling efficacy of NOTCH3 mutant protein remain largely unknown. Here, we found elevated NOTCH3 and Radical fringe (RFNG) expression in senescent human pericyte cells. We then investigated impacts of RFNG on glycosylation, degradation, and signal activity of three NOTCH3 CADASIL mutants (R90C, R141C, and C185R) in EGF-like repeat-2, 3, and 4, respectively. LC–MS/MS analysis showed that RFNG modified NOTCH3 WT and C185R to different degrees. Additionally, coculture experiments demonstrated that RFNG significantly promoted JAG1-dependent degradation of NOTCH3 WT but not that of R141C and C185R mutants. Furthermore, RFNG exhibited a greater inhibitory effect on JAG1-mediated activity of NOTCH3 R141C and C185R compared to that of NOTCH3 WT and R90C. In summary, our findings suggest that NOTCH3 R141C and C185R mutant proteins are relatively susceptible to accumulation and signaling impairment under cellular conditions of RFNG and JAG1 coexistence.
HostingRepository	jPOST
AnnounceDate	2024-09-19
AnnouncementXML	Submission_2024-09-18_21:39:04.700.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Shodai Suzuki
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	S-carboxamidomethyl-L-cysteine; L-methionine sulfoxide
Instrument	Orbitrap Fusion

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2024-01-15 04:12:24	ID requested
⏵ 1	2024-09-18 21:39:05	announced

Publication List

Dataset with its publication pending

Dataset with its publication pending

Keyword List

submitter keyword: CADASIL/Fringe/NOTCH3/O-fucose

submitter keyword: CADASIL/Fringe/NOTCH3/O-fucose

Contact List

Motoyuki Itoh
lab head
Shodai Suzuki
contact affiliation	Chiba University
dataset submitter

Full Dataset Link List

jPOST dataset URI
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jPOST 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://ftp.jpostdb.org/JPST002465/