PXD017279-2

PXD017279 is an original dataset announced via ProteomeXchange.

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

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.

Dataset with its publication pending

submitter keyword: human cytomegalovirus

cell death

necroptosis

host-pathogen interaction

quantitative proteomics

protein degradation

proteasome

MLKL

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

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PRIDE project URI

• PRIDE
  1. PXD017279
     1. Label: PRIDE project
     2. Name: Human cytomegalovirus protein pUL36: a dual cell death pathway inhibitor