PXD017279 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Human cytomegalovirus protein pUL36: a dual cell death pathway inhibitor |
Description | Human cytomegalovirus (HCMV) is an important human pathogen and a paradigm of intrinsic, innate and adaptive viral immune evasion. Here, we employ multiplexed tandem mass tag-based proteomics to characterise host proteins targeted for degradation late during HCMV infection. This approach revealed that mixed lineage kinase domain-like protein (MLKL), a key terminal mediator of cellular necroptosis, was rapidly and persistently degraded by the minimally passaged HCMV strain Merlin but not the extensively passaged strain AD169. The strain Merlin viral inhibitor of apoptosis pUL36 was necessary and sufficient both to degrade MLKL and to inhibit necroptosis. Furthermore, mutation of pUL36 Cys131 abrogated MLKL degradation and restored necroptosis. As the same residue is also required for pUL36-mediated inhibition of apoptosis by preventing proteolytic activation of pro-caspase 8, we define pUL36 as a multifunctional inhibitor of both apoptotic and necroptotic cell death. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_05:08:44.603.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Michael Weekes |
SpeciesList | scientific name: Cytomegalovirus; NCBI TaxID: 10358; scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos; Orbitrap Fusion |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-01-24 08:44:16 | ID requested | |
1 | 2020-07-09 22:39:11 | announced | |
⏵ 2 | 2024-10-22 05:08:45 | announced | 2024-10-22: Updated project metadata. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: human cytomegalovirus |
cell death |
necroptosis |
host-pathogen interaction |
quantitative proteomics |
protein degradation |
proteasome |
MLKL |
Contact List
Michael Weekes |
contact affiliation | Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge, CB2 0XY, UK |
contact email | mpw1001@cam.ac.uk |
lab head | |
Michael Weekes |
contact affiliation | University of Cambridge |
contact email | mpw1001@cam.ac.uk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD017279
- Label: PRIDE project
- Name: Human cytomegalovirus protein pUL36: a dual cell death pathway inhibitor