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PXD019465-2

PXD019465 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleZAP-70 promotes microenvironment interactions and increases protein-translation in chronic lymphocytic leukemia
DescriptionThe expression of ZAP-70 in a subset of CLL patients strongly correlates with a more aggressive clinical course, though the exact underlying mechanisms remain elusive. The ability of ZAP-70 to enhance B cell receptor (BCR) signaling, independently of its kinase function, likely contributes. Here we employed RNA-sequencing and proteomic analyses of primary cells and cell lines, differing only in their expression of ZAP-70, to further define how ZAP-70 increases aggressiveness of CLL. We identified that ZAP-70 is required for the constitutive expression of T cell chemokines and the MHC class I molecule CD1c in the absence of an overt BCR signal, both promoting interactions with T cells. In addition, quantitative mass spectrometry of double-cross linked ZAP-70 complexes demonstrated that direct protein-protein interactions between ZAP-70 and cytoskeletal proteins positively regulate cell migration, irrespectively of CCR7 expression. Importantly, these functions of ZAP-70 did not require antigen-stimulation of the BCR. In contrast, we observed that ZAP-70 rapidly forms complexes with ribosomal proteins in BCR-activated cells, while decreasing the expression of ZAP-70 significantly reduced protein biosynthesis, providing evidences that ZAP-70 contributes to translational dysregulation in CLL. In conclusion, ZAP-70 promotes microenvironment-interactions and protein-translation in CLL cells, both likely to improve cellular fitness and to further drive disease progression.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_08:50:35.200.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterValar Nila Roamio Franklin
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmethylthiolated residue; deaminated residue; monohydroxylated residue
InstrumentOrbitrap Fusion Lumos; LTQ Orbitrap Velos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-05-29 03:19:31ID requested
12022-08-26 06:26:34announced
22023-11-14 08:50:35announced2023-11-14: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: ZAP70, Q-plex_RIME, Leukemia
Contact List
Clive D'Santos
contact affiliationHead of Proteomics CRUK Cambridge Institute Cambridge University Robinson Way Cambridge CB2 0RE UK Email: clive.d’santos@cruk.cam.ac.uk Phone: +44 1223 769677
contact emailsantos@cruk.cam.ac.uk
lab head
Valar Nila Roamio Franklin
contact affiliationResearch Assistant
contact emailValar.Franklin@cruk.cam.ac.uk
dataset submitter
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Dataset FTP location
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