PXD067076

PXD067076 is an original dataset announced via ProteomeXchange.

Title	DCAF11-dependent molecular glue degrader activated by glutathionylation
Description	Targeted protein degradation is a powerful pharmacological strategy that harnesses the ubiquitin proteasome system to eliminate disease-relevant proteins, including otherwise undruggable proteins. Here, we report an unbiased and broadly applicable platform for the systematic discovery of molecular glues across diverse E3 ligases. Using multiplexed mass spectrometry-based chemical screening, we identified a molecular glue, M12, that reprograms the E3 ligase DCAF11 to degrade DDX18. We found that M12 functions as a prodrug, activated by glutathionylation. The glutathione moiety then directly engages DCAF11, enabling neo-substrate recruitment. We demonstrate that this mechanism readily enables targeted degradation of a range of proteins. Our studies highlight a novel approach to redirect E3 ligase function through an enzyme-activated small molecule, expanding the scope of targeted protein degradation and chemically induced proximity.
HostingRepository	PRIDE
AnnounceDate	2026-06-18
AnnouncementXML	Submission_2026-06-18_15:10:58.964.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: NEWT:9606;
ModificationList	iodoacetamide derivatized residue
Instrument	timsTOF Ultra 2

Revision	Datetime	Status	ChangeLog Entry
0	2025-08-07 08:29:51	ID requested
⏵ 1	2026-06-18 15:10:59	announced

Dataset with its publication pending

submitter keyword: None

Eric Fischer
contact affiliation	Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, 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/2026/06/PXD067076

PRIDE project URI

• PRIDE
  1. PXD067076
     1. Label: PRIDE project
     2. Name: DCAF11-dependent molecular glue degrader activated by glutathionylation