Proteomics

Dataset Information

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Human cytomegalovirus protein pUL36: a dual cell death pathway inhibitor


ABSTRACT: 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.

INSTRUMENT(S): Orbitrap Fusion Lumos, Orbitrap Fusion

ORGANISM(S): Homo sapiens   Cytomegalovirus  

TISSUE(S): Cell Culture

DISEASE(S): Not Available

SUBMITTER: Michael Weekes  

LAB HEAD: Michael Weekes

PROVIDER: PXD017279 | Pride | 2020-07-10

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
Fletcher-Etherington et al Peptides.xlsx Xlsx
Fletcher-Etherington et al Proteins.xlsx Xlsx
PRIDE submission - Details of samples.docx Other
WCL1_A1_run1.raw Raw
WCL1_B1_run1.raw Raw
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