PXD042243 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Design of a mucin-selective protease for targeted degradation of cancer-associated mucins |
Description | Targeted protein degradation is an emerging strategy for the elimination of classically undruggable proteins. Here, to expand the landscape of targetable substrates, we designed degraders that achieve substrate selectivity via recognition of a discrete peptide- and glycan- motif and achieve cell-type selectivity via antigen-driven cell surface binding. We applied this approach to mucins, O-glycosylated proteins that drive cancer progression through biophysical and immunological mechanisms. Engineering of a bacterial mucin-selective protease yielded a variant for fusion to a cancer antigen-binding nanobody. The resulting conjugate selectively degraded mucins on cancer cells, promoted cell death in culture models of mucin-driven growth and survival, and reduced tumor growth in murine models of breast cancer progression. This work establishes a blueprint for the development of biologics that degrade specific glycoproteins on target cells. |
HostingRepository | PRIDE |
AnnounceDate | 2023-11-14 |
AnnouncementXML | Submission_2023-11-14_06:39:26.559.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Nicholas Riley |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | complex glycosylation |
Instrument | Orbitrap Fusion |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-05-15 16:13:16 | ID requested | |
1 | 2023-07-21 09:27:40 | announced | |
⏵ 2 | 2023-11-14 06:39:26 | announced | 2023-11-14: Updated project metadata. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: mucins, glycoprotease,Targeted degradation, TAILS |
Contact List
Carolyn R. Bertozzi |
contact affiliation | Department of Chemistry, Stanford University |
contact email | bertozzi@stanford.edu |
lab head | |
Nicholas Riley |
contact affiliation | Stanford University |
contact email | riley.nicholasm@gmail.com |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD042243
- Label: PRIDE project
- Name: Design of a mucin-selective protease for targeted degradation of cancer-associated mucins