PXD019465 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | ZAP-70 promotes microenvironment interactions and increases protein-translation in chronic lymphocytic leukemia |
Description | The 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. |
HostingRepository | PRIDE |
AnnounceDate | 2023-11-14 |
AnnouncementXML | Submission_2023-11-14_08:50:35.200.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Valar Nila Roamio Franklin |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | methylthiolated residue; deaminated residue; monohydroxylated residue |
Instrument | Orbitrap Fusion Lumos; LTQ Orbitrap Velos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-05-29 03:19:31 | ID requested | |
1 | 2022-08-26 06:26:34 | announced | |
⏵ 2 | 2023-11-14 08:50:35 | announced | 2023-11-14: 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 affiliation | Head 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 email | santos@cruk.cam.ac.uk |
lab head | |
Valar Nila Roamio Franklin |
contact affiliation | Research Assistant |
contact email | Valar.Franklin@cruk.cam.ac.uk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD019465
- Label: PRIDE project
- Name: ZAP-70 promotes microenvironment interactions and increases protein-translation in chronic lymphocytic leukemia