PXD065168-1

PXD065168 is an original dataset announced via ProteomeXchange.

Title	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	2025-09-11
AnnouncementXML	Submission_2025-09-10_20:09:38.144.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD065168
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Dylan Mitchell
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-18 09:59:14	ID requested
⏵ 1	2025-09-10 20:09:38	announced

10.6019/PXD065168;

10.1038/s41589-025-02011-1;

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, ():(2025) [pubmed]

submitter keyword: Proteomics, Degradation, Ubiquitin

Dylan Mitchell
contact affiliation	Harvard Medical School
contact email	dylancmitchell@gmail.com
lab head
Dylan Mitchell
contact affiliation	Harvard Medical School
contact email	dylancmitchell@gmail.com
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/PXD065168

PRIDE project URI

• PRIDE
  1. PXD065168
     1. Label: PRIDE project
     2. Name: Ubiquitination of a small molecule