PXD041685

PXD041685 is an original dataset announced via ProteomeXchange.

Title	BioE3 enables the identification of bona fide targets of E3 ligases
Description	The post-translational modification of proteins by ubiquitination is a highly regulated process that involves a dynamic, three-step enzymatic cascade, where more than 600 E3 ligases play a critical role in recognizing specific substrates for modification. Separating bona fide targets of E3s from E3-interacting proteins remains a major challenge in the field. In this study, we present BioE3, a novel approach for identifying substrates of ubiquitin-like (UbL) E3 ligases of interest. Using BirA-E3 ligase fusion proteins and bioUbLs, the method facilitates site-specific biotinylation of UbL-modified substrates for proteomic identification. We demonstrate that the BioE3 system can identify both known and novel targets of two RING-type ubiquitin E3 ligases: RNF4, known to be involved in DNA damage response and the regulation of PML nuclear bodies, and MIB1, implicated in endocytosis, autophagy, and centrosomal protein homeostasis. We further show the versatility of BioE3 by identifying targets of an organelle-specific E3 (MARCH5) and a relatively uncharacterized E3 (RNF214). Furthermore, we show that BioE3 works with HECT-type E3 ligases and identify novel targets of NEDD4 involved in vesicular trafficking. BioE3 is a powerful tool that enables identification of bona fide substrates of UbL E3 ligases and how they change with chemical perturbations, which may be useful for the emerging applications in targeted protein degradation (TPD). BioE3 may also be applicable for UbLs beyond Ub and SUMO, as well as other E3 ligase classes. The resulting knowledge can shed light on the regulation of cellular processes by the complex UbL network, advancing our understanding of fundamental biological mechanisms.
HostingRepository	PRIDE
AnnounceDate	2024-01-26
AnnouncementXML	Submission_2024-01-26_13:42:54.379.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ibon Iloro
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	ubiquitinylated lysine
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2023-04-20 07:42:11	ID requested
⏵ 1	2024-01-26 13:42:55	announced

Barroso-Gomila O, Merino-Cacho L, Muratore V, Perez C, Taibi V, Maspero E, Azkargorta M, Iloro I, Trulsson F, Vertegaal ACO, Mayor U, Elortza F, Polo S, Barrio R, Sutherland JD, BioE3 identifies specific substrates of ubiquitin E3 ligases. Nat Commun, 14(1):7656(2023) [pubmed]

10.1038/s41467-023-43326-8;

submitter keyword: E3-ligases,BioE3, ubiquitination, Proteomics

James D. Sutherland
contact affiliation	Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Building 801A, 48160 Derio, Spain.
contact email	jsutherland@cicbiogune.es
lab head
Ibon Iloro
contact affiliation	CIC bioGUNE
contact email	iiloro@cicbiogune.es
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/2024/01/PXD041685

PRIDE project URI

• PRIDE
  1. PXD041685
     1. Label: PRIDE project
     2. Name: BioE3 enables the identification of bona fide targets of E3 ligases