PXD048931-2

PXD048931 is an original dataset announced via ProteomeXchange.

Title	Degradome analysis to identify direct substrates of small-molecule protein degraders
Description	Targeted protein degradation (TPD) has emerged as a powerful strategy to selectively eliminate cellular proteins using small-molecule degraders, offering therapeutic promise for targeting proteins that are otherwise undruggable. However, a remaining challenge is to unambiguously identify primary TPD targets that are distinct from secondary downstream effects in the proteome. Here we introduce an approach that combines stable isotope labeling and click-chemistry for selective quantification of protein degradation by mass spectrometry, excluding confounding effects of altered transcription and translation induced by target depletion. We show that the approach efficiently operates at the time scale of TPD (hours) and we demonstrate its utility by analyzing the Cyclin K degraders dCeMM2 and dCeMM4, which induce widespread transcriptional downregulation, and the GSPT1 degrader CC-885, an inhibitor of protein translation. Additionally, we apply it to characterize compound 1, a previously uncharacterized degrader, and identify the zinc-finger protein FIZ1 as a degraded target.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_07:01:47.852.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Lina-Marie Wagner
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-01-26 21:08:35	ID requested
1	2024-10-15 01:50:11	announced
⏵ 2	2024-10-22 07:01:48	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: TPD, SILAC labelling, degradomics

Jeroen Krijgsveld
contact affiliation	German Cancer Research Center, Division Proteomics of Stem Cells and Cancer, Heidelberg, Germany Heidelberg University, Medical Faculty, Heidelberg, Germany
contact email	j.krijgsveld@dkfz.de
lab head
Lina-Marie Wagner
contact affiliation	German Cancer Research Center
contact email	lina-marie.wagner@dkfz-heidelberg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD048931
     1. Label: PRIDE project
     2. Name: Degradome analysis to identify direct substrates of small-molecule protein degraders