PXD023579-2

PXD023579 is an original dataset announced via ProteomeXchange.

Title	K27-linked ubiquitylation promotes p97 substrate processing and is essential for cell proliferation
Description	Conjugation of ubiquitin (Ub) to numerous substrate proteins regulates virtually all cellular processes. Eight distinct ubiquitin polymer linkages specifying different functional outcomes are generated in cells. However, the roles of some atypical poly-ubiquitin topologies, in particular linkages via lysine 27 (K27), remain poorly understood due to a lack of tools for their specific detection and manipulation. Here, we adapted a cell-based ubiquitin replacement strategy to enable selective and conditional abrogation of K27-linked ubiquitylation, revealing that this ubiquitin linkage type is essential for proliferation of human cells. We demonstrate that K27-linked ubiquitylation is predominantly a nuclear modification whose ablation deregulates nuclear ubiquitylation dynamics and impairs cell cycle progression in an epistatic manner with inactivation of the ATPase p97/VCP. Moreover, we show that a p97-proteasome pathway model substrate (Ub(G76V)-GFP) is directly modified by K27-linked ubiquitylation, and that disabling the formation of K27-linked ubiquitin signals or blocking their decoding via overexpression of the K27 linkage-specific binder UCHL3 impedes Ub(G76V)-GFP turnover at the level of p97 function. Our findings suggest a critical role of K27-linked ubiquitylation in supporting cell fitness by facilitating p97-dependent processing of ubiquitylated nuclear proteins.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:30:04.871.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Fabian Coscia
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	ubiquitinylated lysine
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-01-14 00:18:16	ID requested
1	2022-04-14 14:18:25	announced
⏵ 2	2023-11-14 08:30:05	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: Ubiquitin, Proteomics, K27

Niels Mailand
contact affiliation	Protein Signaling Program, Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, DK-2200 Copenhagen, Denmark
contact email	niels.mailand@cpr.ku.dk
lab head
Fabian Coscia
contact affiliation	Max Delbrueck Center for Molecular Medicine
contact email	fabian.coscia@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/2022/04/PXD023579

PRIDE project URI

• PRIDE
  1. PXD023579
     1. Label: PRIDE project
     2. Name: K27-linked ubiquitylation promotes p97 substrate processing and is essential for cell proliferation