PXD044082 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | ADAM17 targeting by human cytomegalovirus remodels the cell surface proteome to simultaneously regulate multiple immune pathways |
Description | Human cytomegalovirus (HCMV) is a major human pathogen whose life-long persistence is enabled by its remarkable capacity to systematically subvert host immune defences. In exploring the finding that HCMV infection upregulates tumor necrosis factor receptor 2 (TNFR2), a ligand for the proinflammatory anti-viral cytokine TNFa, we discovered the underlying mechanism was due to targeting of the protease, A Disintegrin And Metalloproteinase 17 (ADAM17). ADAM17 is the prototype ‘sheddase, a family of proteases that cleaves other membrane-bound proteins to release biologically active ectodomains into the supernatant. HCMV impaired ADAM17 surface expression through the action of two virally-encoded proteins in its UL/b’ region, UL148 and UL148D. Proteomic plasma membrane profiling of cells infected with a HCMV double deletion mutant for UL148 and UL148D with restored ADAM17 expression, combined with ADAM17 functional blockade, showed that HCMV stabilized the surface expression of 114 proteins (p<0.05) in an ADAM17-dependent fashion. These included known substrates of ADAM17 with established immunological functions such as TNFR2 and Jagged1, but also numerous novel host and viral targets, such as Nectin1, UL8 and UL144. Regulation of TNFa-induced cytokine responses and NK inhibition during HCMV infection were dependent on this impairment of ADAM17. We therefore identify a viral immunoregulatory mechanism in which targeting a single sheddase enables broad regulation of multiple critical surface receptors, revealing a paradigm for viral-encoded immunomodulation. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_06:05:38.835.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Michael Weekes |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; scientific name: Cytomegalovirus; NCBI TaxID: NCBITaxon:10358; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-07-25 13:37:55 | ID requested | |
1 | 2023-10-11 07:08:54 | announced | |
2 | 2023-11-14 09:06:01 | announced | 2023-11-14: Updated project metadata. |
⏵ 3 | 2024-10-22 06:05:39 | announced | 2024-10-22: Updated project metadata. |
Publication List
Rubina A, Patel M, Nightingale K, Potts M, Fielding CA, Kollnberger S, Lau B, Ladell K, Miners KL, Nichols J, Nobre L, Roberts D, Trinca TM, Twohig JP, Vlahava VM, Davison AJ, Price DA, Tomasec P, Wilkinson GWG, Weekes MP, Stanton RJ, Wang ECY, ADAM17 targeting by human cytomegalovirus remodels the cell surface proteome to simultaneously regulate multiple immune pathways. Proc Natl Acad Sci U S A, 120(33):e2303155120(2023) [pubmed] |
10.1073/pnas.2303155120; |
Keyword List
submitter keyword: UL148, TNFR2, immune, ADAM17, Natural killer cell,Human cytomegalovirus |
Contact List
Michael Weekes |
contact affiliation | Cambridge Institute for Medical Research, University of Cambridge |
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
- PXD044082
- Label: PRIDE project
- Name: ADAM17 targeting by human cytomegalovirus remodels the cell surface proteome to simultaneously regulate multiple immune pathways