PXD053243

PXD053243 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	Highly-specific intracellular ubiquitination of a small molecule
Description	Ubiquitin is a small, highly conserved protein that acts as a post-translational modification in eukaryotes. Ubiquitination of proteins frequently serves as a degradation signal, marking them for disposal by the proteasomal. Here, we report a novel small molecule from a diversity- oriented synthesis library, BRD1732, that is directly ubiquitinated in cells, resulting in dramatic accumulation of unproductive ubiquitin monomer and polyubiquitin chains and broad inhibition of the ubiquitin-proteasome system. Ubiquitination of BRD1732 and its associated cytotoxicity are stereospecific and dependent upon two homologous E3 ubiquitin ligases, RNF19A and RNF19B. Our finding opens a possibility for indirect ubiquitination of a target through a ubiquitinated bifunctional small molecule, and more broadly raises the potential for post- translational modification in trans.
HostingRepository	PRIDE
AnnounceDate	2026-04-06
AnnouncementXML	Submission_2026-04-05_16:15:08.583.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD053243
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Joel Chick
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	carbamoylated residue; monohydroxylated residue
Instrument	Orbitrap Fusion Lumos

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-19 19:30:54	ID requested
⏵ 1	2026-04-05 16:15:09	announced

Publication List

10.1038/s41589-025-02011-1;
10.6019/PXD053243;
Li W, Garcia-Rivera EM, Mitchell DC, Chick JM, Maetani M, Bhadoria R, Knapp JM, Misu R, Matthews GM, Shirasaki R, de Matos Simoes R, Viswanathan V, Pulice JL, Rees MG, Roth JA, Gygi SP, Mitsiades CS, Kadoch C, Schreiber SL, Ostrem JML, Highly specific intracellular ubiquitination of a small molecule. Nat Chem Biol, 22(4):663-671(2026) [pubmed]

10.1038/s41589-025-02011-1;

10.6019/PXD053243;

Li W, Garcia-Rivera EM, Mitchell DC, Chick JM, Maetani M, Bhadoria R, Knapp JM, Misu R, Matthews GM, Shirasaki R, de Matos Simoes R, Viswanathan V, Pulice JL, Rees MG, Roth JA, Gygi SP, Mitsiades CS, Kadoch C, Schreiber SL, Ostrem JML, Highly specific intracellular ubiquitination of a small molecule. Nat Chem Biol, 22(4):663-671(2026) [pubmed]

Keyword List

submitter keyword: Proteomics, Degradation, Ubiquitin

submitter keyword: Proteomics, Degradation, Ubiquitin

Contact List

Steve Gygi
contact affiliation	Harvard Medical School
contact email	steven_gygi@hms.harvard.edu
lab head
Joel Chick
contact affiliation	Harvard Medical School
contact email	chick.joel@gmail.com
dataset submitter

Full Dataset Link List

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/2026/04/PXD053243
PRIDE project URI

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/2026/04/PXD053243

PRIDE project URI

Repository Record List

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