PXD040769

PXD040769 is an original dataset announced via ProteomeXchange.

Title	Functional genomics identifies extension of complex N-glycans as a mechanism to evade lysis by natural killer cells
Description	Somatic mutations can lead to the transformation of healthy cells into malignant cells and allow their evasion from immune surveillance. To uncover genes that play a role in the detection and lysis of tumor cells by natural killer (NK) cells, a B lymphoblastoid cell line was subjected to a genome-wide CRISPR screen. Deletion of genes for death receptor and ligands for NK activation receptors was found in cells that survived incubation with primary NK cells. Among the top hits that facilitated NK evasion was SPPL3, a gene for an endoprotease that cleaves transmembrane glycosyl transferases. SPPL3-deficient cells accumulated glycosyl transferases, such as MGAT5, and displayed increased N-glycosylation. Binding of NK receptors NKG2D and CD2 to their corresponding ligands MICB and CD58, and binding of rituximab to CD20, was disrupted. Inhibition of N-glycan maturation restored receptor binding and sensitivity to NK cells. To investigate the cause of this resistant phenotype, a secondary CRISPR screen using a glycosylation-focused library was performed in SPPL3-deficient cells. This screen identified transferases that promote the formation of highly branched N-glycans and N-acetyl-lactosamine (LacNAc) extensions as key regulators that prevent killing. A significant enrichment of poly-LacNAc-containing tetra-antennary species was confirmed by glycoproteomic analysis. These findings provide a basis for understanding why SPPL3 deletions have been linked to cancer.
HostingRepository	PRIDE
AnnounceDate	2024-03-19
AnnouncementXML	Submission_2024-03-19_14:44:28.805.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yanlong Ji
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-10 06:33:04	ID requested
⏵ 1	2024-03-19 14:44:29	announced

Dataset with its publication pending

submitter keyword: N-glycan, SPPL3,natual killer cells, rituximab

Henning Urlaub
contact affiliation	Bioanalytical Mass Spectrometry Group, Max Planck Institute for Multidisciplinary Sciences, 37077 Göttingen, Germany
contact email	henning.urlaub@mpinat.mpg.de
lab head
Yanlong Ji
contact affiliation	Max-Planck-Institute for Multidisciplinary Sciences
contact email	yanlong.ji@mpibpc.mpg.de
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/2024/03/PXD040769

PRIDE project URI

• PRIDE
  1. PXD040769
     1. Label: PRIDE project
     2. Name: Functional genomics identifies extension of complex N-glycans as a mechanism to evade lysis by natural killer cells