PXD021961

PXD021961 is an original dataset announced via ProteomeXchange.

Title	Rapid degradation pathways of host proteins during HCMV infection revealed by quantitative proteomics
Description	Human cytomegalovirus is an important pathogen in immunocompromised individuals and neonates, and a paradigm for viral immune evasion. We previously developed a quantitative proteomic approach that identified 133 proteins degraded during the early phase of HCMV infection, including known and novel antiviral factors. The majority were rescued from degradation by MG132, which is known to inhibit lysosomal cathepsins in addition to the proteasome. Global definition of the precise mechanisms of host protein degradation is important both to improve our understanding of viral biology, and to inform novel antiviral therapeutic strategies. We therefore developed and optimised a multiplexed comparative proteomic analysis using the selective proteasome inhibitor bortezomib in addition to MG132, to provide a global mechanistic view of protein degradation. Of proteins rescued from degradation by MG132, 62-85% were also rescued by bortezomib, suggesting both that the predominant mechanism of protein degradation employed by HCMV is via the proteasome, and that alternative pathways for degradation are nevertheless important. Our approach and data will enable improved mechanistic understanding of HCMV and other viruses, and provide a shortlist of candidate restriction factors for further analysis.
HostingRepository	PRIDE
AnnounceDate	2021-01-08
AnnouncementXML	Submission_2021-01-08_00:02:37.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kai-Min Lin
SpeciesList	scientific name: Cytomegalovirus; NCBI TaxID: 10358; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex reporter+balance reagent O-acylated residue; monohydroxylated residue; iodoacetamide derivatized amino-terminal residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2020-10-14 01:33:37	ID requested
⏵ 1	2021-01-08 00:02:37	announced

Dataset with its publication pending

submitter keyword: Human, HCMV, proteasome, MG132, Bortezomib, TMT, LC-MS3

Michael Weekes
contact affiliation	Cambridge Institute for Medical Research, University of Cambridge
contact email	mpw1001@cam.ac.uk
lab head
Kai-Min Lin
contact affiliation	Cambridge Institue for Medical Research, University of Cambridge
contact email	kml53@cam.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD021961
     1. Label: PRIDE project
     2. Name: Rapid degradation pathways of host proteins during HCMV infection revealed by quantitative proteomics