PXD051470-1

PXD051470 is an original dataset announced via ProteomeXchange.

Title	N-terminomics profiling of naive and inflamed murine colon reveals proteolytic signals of legumain
Description	Legumain is a cysteine protease broadly associated with inflammation. It has recently been reported to cleave and activate protease-activated receptor 2 to provoke pain associated with oral cancer. Outside of gastric and colon cancer, little has been reported on the roles of legumain within the gastrointestinal tract. Using a legumain-selective activity-based probe, LE28, we report that legumain is activated within colonocytes and macrophages of the murine colon, and that it is upregulated in models of acute experimental colitis induced by DSS and TNBS. We demonstrated that loss of legumain activity in colonocytes, either through pharmacological inhibition or gene deletion, had no impact on epithelial permeability in vitro. Moreover, legumain inhibition or deletion had no obvious impacts on symptoms or histological features associated with DSS-induced colitis, suggesting its proteolytic activity is dispensable for colitis initiation. To gain insight into potential functions of legumain within the colon, we performed FAIMS-facilitated quantitative proteomics and N-terminomics analyses on naïve and inflamed colon tissue from wild-type and legumain-deficient mice. We identified 16 altered cleavage sites with an asparaginyl endopeptidase signature that may be direct substrates of legumain and a further 16 cleavage sites that may be indirectly mediated by legumain. We also analyzed changes in protein abundance and proteolytic events broadly associated with colitis in the gut, which permitted comparison to recent analyses on mucosal biopsies from patients with inflammatory bowel disease. Collectively, these results shed light on potential functions of legumain and highlight its potential roles in the transition from inflammation to colorectal cancer.
HostingRepository	PRIDE
AnnounceDate	2025-09-29
AnnouncementXML	Submission_2025-09-28_16:17:25.923.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alexander Ziegler
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-15 22:12:45	ID requested
⏵ 1	2025-09-28 16:17:26	announced

10.1002/pro.70186;

Ziegler AR, Parker BL, Scott NE, Edgington-Mitchell LE, ve and inflamed colon tissue. Protein Sci, 34(10):e70186(2025) [pubmed]

submitter keyword: protease,N-terminomics, legumain, colon, colitis

Laura E Edgington-Mitchell
contact affiliation	Department of Biochemistry and Pharmacology, Bio21 Institute, University of Melbourne
contact email	laura.edgingtonmitchell@unimelb.edu.au
lab head
Alexander Ziegler
contact affiliation	University of Melbourne
contact email	azzi@student.unimelb.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD051470
     1. Label: PRIDE project
     2. Name: N-terminomics profiling of naive and inflamed murine colon reveals proteolytic signals of legumain