PXD003936

PXD003936 is an original dataset announced via ProteomeXchange.

Title	Proteomic profiling of VCP substrates links VCP to K6-linked ubiquitylation and c-Myc function
Description	VCP is an evolutionary conserved ubiquitin-dependent ATPase that mediates the degradation of proteins through the ubiquitin-proteasome pathway. Despite the central role of VCP in the regulation of protein homeostasis, identity and nature of its cellular substrates remain poorly defined. Here, we combined chemical inhibition of VCP and quantitative ubiquitin remnant profiling to assess the effect of VCP inhibition on the ubiquitin-modified proteome and to probe the substrate spectrum of VCP in human cells. We demonstrate that inhibition of VCP perturbs cellular ubiquitylation and increases ubiquitylation of a different subset of proteins compared to proteasome inhibition. VCP inhibition globally upregulates K6-linked ubiquitylation that is dependent on the HECT-type ubiquitin E3 ligase HUWE1. We report ~450 putative VCP substrates, many of which function in nuclear processes, including gene expression, DNA repair and cell cycle. Moreover, we identify that VCP regulates the level and activity of the transcription factor c-Myc.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:04:44.351.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Petra Beli
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	ubiquitinylated lysine
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2016-04-10 23:54:48	ID requested
1	2018-02-09 11:29:37	announced
2	2018-02-14 02:01:01	announced	Updated project metadata.
3	2019-02-12 08:07:14	announced	Updated project metadata.
⏵ 4	2024-10-22 04:04:52	announced	2024-10-22: Updated project metadata.

10.15252/embr.201744754;

curator keyword: Biological

submitter keyword: ubiquitin-proteasome system, ubiquitin remnant profiling, quantitative mass spectrometry,Protein homeostasis, VCP

Petra Beli
contact affiliation	Institute of Molecular Biology (IMB), Mainz, Germany
contact email	p.beli@imb-mainz.de
lab head
Petra Beli
contact affiliation	Institute of Molecular Biology (IMB), Mainz, Germany
contact email	p.beli@imb-mainz.de
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/2018/02/PXD003936

PRIDE project URI

• PRIDE
  1. PXD003936
     1. Label: PRIDE project
     2. Name: Proteomic profiling of VCP substrates links VCP to K6-linked ubiquitylation and c-Myc function