PXD042086

PXD042086 is an original dataset announced via ProteomeXchange.

Title	Profiling ubiquitin signaling with UBIMAX reveals DNA damage- and SCFβTRCP-dependent ubiquitylation of the actin-organizing protein Dbn1
Description	Ubiquitin widely modifies proteins, thereby regulating most cellular functions. The complexity of ubiquitin signalling necessitates unbiased methods enabling global detection of dynamic protein ubiquitylation. Here, we describe UBIMAX (UBiquitin target Identification by Mass spectrometry in Xenopus egg extracts), which enriches ubiquitin-conjugated proteins and quantifies regulation of protein ubiquitylation under precise and adaptable conditions. We benchmark UBIMAX by investigating DNA double-strand break-responsive ubiquitylation events, identifying previously known targets and revealing the actin-organising protein Dbn1 as a novel major target of DNA damage-induced ubiquitylation. We find that Dbn1 is targeted for proteasomal degradation by the SCFβ-Trcp1 ubiquitin ligase, in a conserved mechanism driven by ATM-mediated phosphorylation of a previously uncharacterized β-Trcp1 degron containing an SQ motif. We further show that this degron is sufficient to induce DNA-damage dependent protein degradation of a model substrate. Collectively, we demonstrate UBIMAX’s ability to identify novel targets of stimulus-regulated ubiquitylation and reveal an SCFβ-Trcp1-mediated ubiquitylation mechanism controlled directly by the apical DNA damage response kinases.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:17:42.552.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Camilla Colding-Christensen
SpeciesList	scientific name: Xenopus laevis (African clawed frog); NCBI TaxID: 8355;
ModificationList	ubiquitinylated lysine; phosphorylated residue
Instrument	Orbitrap Exploris 480; Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-09 06:22:47	ID requested
1	2023-12-14 08:20:42	announced
⏵ 2	2024-10-22 06:17:42	announced	2024-10-22: Updated project metadata.

10.1038/S41467-023-43873-0;

submitter keyword: Ubiquitin, degron, βTRCP1, DBN1, ATM, DNA-protein crosslinks, actin, SCF, DNA double-strand breaks, protein degradation, DNA damage, DNA damage response

Michael Lund Nielsen
contact affiliation	Proteomics program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark
contact email	michael.lund.nielsen@cpr.ku.dk
lab head
Camilla Colding-Christensen
contact affiliation	Proteomics program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen
contact email	camilla.colding@cpr.ku.dk
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/2023/12/PXD042086

PRIDE project URI

• PRIDE
  1. PXD042086
     1. Label: PRIDE project
     2. Name: Profiling ubiquitin signaling with UBIMAX reveals DNA damage- and SCFβTRCP-dependent ubiquitylation of the actin-organizing protein Dbn1