PXD019465-2

PXD019465 is an original dataset announced via ProteomeXchange.

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

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.

Dataset with its publication pending

submitter keyword: ZAP70, Q-plex_RIME, Leukemia

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/08/PXD019465

PRIDE project URI

• PRIDE
  1. PXD019465
     1. Label: PRIDE project
     2. Name: ZAP-70 promotes microenvironment interactions and increases protein-translation in chronic lymphocytic leukemia