PXD067088

PXD067088 is an original dataset announced via ProteomeXchange.

Title	Ubiquitin profiling of drug-like small molecule-treated cells
Description	The ubiquitin system regulates eukaryotic physiology by modifying specific substrate proteins. Substrate recognition and the assembly of ubiquitin signals are determined by ubiquitin ligases, some of which also modify non-protein biomolecules. Here we expand this substrate realm, revealing that the human ligase HUWE1 can target drug-like small molecules. We demonstrate that compounds previously reported as HUWE1 inhibitors present substrates of their target ligase. Compound ubiquitination is driven by the canonical catalytic cascade, linking ubiquitin to the compound’s primary amino group. In vitro, the modification is selectively catalyzed by HUWE1, allowing the compounds to compete with protein substrates. We establish cellular detection methods, confirming HUWE1 promotes — but does not exclusively drive — compound ubiquitination in cells.
HostingRepository	PRIDE
AnnounceDate	2025-09-10
AnnouncementXML	Submission_2025-09-10_05:22:56.947.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christian Behrends
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	carbamoylated residue; acetylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-08-07 13:20:22	ID requested
⏵ 1	2025-09-10 05:22:57	announced

10.1038/s41467-025-63442-x;

Orth B, Pohl P, Aust F, Ji Y, Seenivasan A, Dybkov O, Liang XJ, Bock L, Leidner F, Levantovsky S, Schardey P, Sander P, Disch NJ, Trautz ML, Mizi A, Papantonis A, Lenz C, Grubm, ü, ller H, Steinchen W, Behrends C, Urlaub H, Gehringer M, Lorenz S, Selective ubiquitination of drug-like small molecules by the ubiquitin ligase HUWE1. Nat Commun, 16(1):8182(2025) [pubmed]

submitter keyword: drug-like small molecules,diGly, Ubiquitin, HUWE1

Christian Behrends
contact affiliation	Munich Cluster for Systems Neurology (SyNergy), Faculty of Medicine, Ludwig-Maximilians University München, Munich, Germany
contact email	christian.behrends@mail03.med.uni-muienchen.de
lab head
Christian Behrends
contact affiliation	SyNergy, LMU München
contact email	christian.behrends@mail03.med.uni-muenchen.de
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/2025/09/PXD067088

PRIDE project URI

• PRIDE
  1. PXD067088
     1. Label: PRIDE project
     2. Name: Ubiquitin profiling of drug-like small molecule-treated cells