PXD034378 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Exploring Effectiveness of KEAP1-based PROTAC Strategy |
Description | Targeted protein degradation (TPD) uses small molecules to recruit E3 ubiquitin ligases into proximity of proteins of interest, inducing ubiquitination-dependent degradation. A major bottleneck in the TPD field is the lack of accessible E3 ligase ligands for developing degraders. To expand the E3 ligase toolbox, we sought to convert the KEAP1 inhibitor KI696 into a recruitment handle for several targets. While we were able to generate KEAP1-recruiting degraders of BET family and murine FAK we discovered that the target scope of KEAP1 was narrow, as targets easily degraded by a cereblon (CRBN)-recruiting degrader were refractory to KEAP1-mediated degradation. Linking the KEAP1-binding ligand to a CRBN-binding ligand resulted in a molecule that induced degradation of KEAP1 but not CRBN. In sum, we characterize tool compounds to explore KEAP1-mediated ubiquitination and delineate the challenges of exploiting new E3 ligases for generating bivalent degraders. |
HostingRepository | PRIDE |
AnnounceDate | 2022-09-07 |
AnnouncementXML | Submission_2022-09-07_12:07:00.057.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Eric Fischer |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | TMT6plex-126 reporter+balance reagent acylated residue; acetylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-06-06 07:20:55 | ID requested | |
⏵ 1 | 2022-09-07 12:07:00 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Targeted Protein Degradation, Degrader, KEAP1, BRD4, FAK |
Contact List
Eric Fischer |
contact affiliation | Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02215, USA |
contact email | eric_fischer@dfci.harvard.edu |
lab head | |
Eric Fischer |
contact affiliation | Dana-Farber Cancer Institute |
contact email | eric_fischer@dfci.harvard.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD034378
- Label: PRIDE project
- Name: Exploring Effectiveness of KEAP1-based PROTAC Strategy