PXD023579-1

PXD023579 is an original dataset announced via ProteomeXchange.

Title	K27-linked ubiquitylation promotes nuclear p97 functions and is essential for cell fitness
Description	Conjugation of the polypeptide ubiquitin (Ub) to numerous substrate proteins impacts and regulates virtually all cellular processes. Eight distinct Ub polymer linkages specifying different functional outcomes are generated in cells, yet the roles of some atypical poly-Ub topologies, in particular K27-linked Ub chains, remain poorly understood due to a lack of tools for specific detection of these low-abundant linkages. Here, we utilized a Ub replacement strategy enabling chemically inducible disruption of individual Ub linkage types to demonstrate that K27-linked Ub chains are essential for proliferation and viability of human cells. We show that K27 linkages are predominantly a nuclear modification and that disabling their formation deregulates cell cycle progression and responses to DNA damage in a manner that is epistatic with inactivation of the ATPase p97. Consistently, targeted ablation of K27-linked Ub chain generation alters the functional status of nuclear p97 complexes and impairs p97 activity. Our findings establish a critical role of K27-linked ubiquitylation in supporting cell proliferation and implicate this enigmatic Ub modification in p97-dependent processing of ubiquitylated client proteins in the nucleus.
HostingRepository	PRIDE
AnnounceDate	2022-04-14
AnnouncementXML	Submission_2022-04-14_14:18:25.350.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.

10.15252/EMBJ.2021110145;

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	University of Copenhagen NNF Center for Protein Research
contact email	fabian.coscia@cpr.ku.dk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD023579
     1. Label: PRIDE project
     2. Name: K27-linked ubiquitylation promotes nuclear p97 functions and is essential for cell fitness