PXD034423

PXD034423 is an original dataset announced via ProteomeXchange.

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	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:57:04.217.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Eric Fischer
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-06-09 13:27:32	ID requested
1	2022-09-07 12:05:59	announced
⏵ 2	2023-11-14 08:57:04	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: BRD4,Targeted Protein Degradation, KEAP1, Degrader, FAK

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

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/2022/09/PXD034423

PRIDE project URI

• PRIDE
  1. PXD034423
     1. Label: PRIDE project
     2. Name: Exploring Effectiveness of KEAP1-based PROTAC Strategy