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PXD057173

PXD057173 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleNEDD4L mediates intestinal epithelial cell ferroptosis to restrict inflammatory bowel diseases and colorectal tumorigenesis
DescriptionVarious factors play key roles in maintaining intestine homeostasis. Disruption of the balance may lead to intestinal inflammatory diseases (IBDs) and even colorectal cancer (CRC). Loss or gain of function of many key proteins can result in dysregulated intestinal homeostasis. Our research demonstrated that neural precursor cells expressed developmentally down-regulated 4-like protein (NEDD4L or NEDD4-2), a type of HECT family E3 ubiquitin ligase, played an important role in maintaining intestinal homeostasis. NEDD4L expression was significantly inhibited in intestinal epithelial cells (IECs) of patients with Crohn's disease (CD), ulcerative colitis (UC), and CRC. Global knockout of NEDD4L or its deficiency in IECs exacerbated dextran sulfate sodium (DSS)-/2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis and azoxymethane (AOM)/DSS-induced colorectal cancer. Mechanistically, NEDD4L deficiency in IECs inhibited the key ferroptosis regulator glutathione peroxidase 4 (GPX4) expression by reducing the protein expression of solute carrier family 3 member 2 (SLC3A2) without affecting its gene expression, ultimately promoting DSS-induced IEC ferroptosis. Importantly, ferroptosis inhibitors reduced the susceptibility of NEDD4L-deficient mice to colitis and colitis-associated colorectal cancer (CAC). Thus, NEDD4L is an important regulator in IEC ferroptosis, maintaining intestinal homeostasis, making it a potential clinical target for diagnosing and treating IBDs.
HostingRepositoryiProX
AnnounceDate2024-10-24
AnnouncementXMLSubmission_2025-10-29_00:43:52.550.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterWenlong Lin
SpeciesList scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-10-24 20:40:46ID requested
12025-10-29 00:43:53announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: NEDD4L, colitis
Contact List
Wenlong Lin
contact affiliationZhejiang University
contact emaillwl210@foxmail.com
lab head
Wenlong Lin
contact affiliationZhejiang University
contact emaillwl210@foxmail.com
dataset submitter
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iProX dataset URI