PXD066969-1

PXD066969 is an original dataset announced via ProteomeXchange.

Title	Identification of Fzd9b ubiquitination
Description	Wnt signaling is critical for the development and maintenance of many cell lineages, including hematopoietic stem cells (HSCs). Tight regulation of Wnt signals is essential, as overactivation can drive tumorigenesis. Numerous Wnt ligands and Frizzled (Fzd) receptors exist, and the negative regulation of particular Fzd signals is the focus of this study. We previously identified the requirement of Wnt9a-Fzd9b pairing for early HSC proliferation. However, the mechanisms controlling activation and signal termination are unclear. Here, we show that the E3 ubiquitin ligase Trip12 (thyroid hormone receptor interactor 12) targets the third intracellular loop of Fzd9b at K437, promoting lysosomal degradation by destabilizing Fzd9b membrane expression. Our data further indicates that Trip12 is semi-selective for Fzd9b. Trip12-mediated reduction of Fzd9b surface expression dampens Wnt9a/Fzd9b signaling, affecting HSC proliferation in zebrafish. Our findings reveal a receptor-specific regulatory mechanism, with implications for targeted Wnt pathway therapies.
HostingRepository	PRIDE
AnnounceDate	2025-08-08
AnnouncementXML	Submission_2025-08-08_00:20:04.124.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hyoungjoo Lee
SpeciesList	scientific name: Helicobacter pylori J99 (Campylobacter pylori J99); NCBI TaxID: 85963; scientific name: Danio rerio (Zebrafish) (Brachydanio rerio); NCBI TaxID: 7955;
ModificationList	ubiquitinylated lysine
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-08-05 03:04:26	ID requested
⏵ 1	2025-08-08 00:20:04	announced

Dataset with its publication pending

submitter keyword: Fzd,ubiquitination, Fzd9b, Frizzled

Stephanie Grainge
contact affiliation	Assistant Professor, Department of Cell Biology Van Andel Institute
contact email	Stephanie.Grainger@vai.org
lab head
Hyoungjoo Lee
contact affiliation	Van Andel Institute
contact email	hyoungjoo.lee@vai.org
dataset submitter

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.pride.ebi.ac.uk/pride/data/archive/2025/08/PXD066969

PRIDE project URI

• PRIDE
  1. PXD066969
     1. Label: PRIDE project
     2. Name: Identification of Fzd9b ubiquitination