PXD031532

PXD031532 is an original dataset announced via ProteomeXchange.

Title	CRISPR activation screen identifies BCL-2 proteins and B3GNT2 as drivers of cancer resistance to T cell-mediated cytotoxicity
Description	The cellular processes that govern tumor resistance to immunotherapy remain poorly understood. To gain insight into these processes, we perform a genome-scale CRISPR activation screen for genes that enable human melanoma cells to evade cytotoxic T cell killing. Overexpression of four top candidate genes (CD274 (PD-L1), MCL1, JUNB, and B3GNT2) confer resistance in diverse cancer cell types and mouse xenografts. By investigating the resistance mechanisms, we find that MCL1 and JUNB modulate the mitochondrial apoptosis pathway. JUNB encodes a transcription factor that downregulates FasL and TRAIL receptors, upregulates the MCL1 relative BCL2A1, and activates the NF-B pathway. B3GNT2 encodes a poly-N-acetyllactosamine synthase that targets >10 ligands and receptors to disrupt interactions between tumor and T cells and reduce T cell activation. Inhibition of candidate genes sensitize tumor models to T cell cytotoxicity. Our results demonstrate that systematic gain-of-function screening can elucidate resistance pathways and identify potential targets for cancer immunotherapy.
HostingRepository	PRIDE
AnnounceDate	2022-02-09
AnnouncementXML	Submission_2022-02-09_05:48:20.725.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD031532
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Julia Joung
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2022-02-09 05:19:58	ID requested
⏵ 1	2022-02-09 05:48:21	announced

Dataset with its publication pending

submitter keyword: B3GNT2, melanoma, co-IP, shotgun proteomics

Feng Zhang
contact affiliation	Broad Institute
contact email	zhang@broadinstitute.org
lab head
Julia Joung
contact affiliation	MIT
contact email	joung@mit.edu
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/2022/02/PXD031532

PRIDE project URI

• PRIDE
  1. PXD031532
     1. Label: PRIDE project
     2. Name: CRISPR activation screen identifies BCL-2 proteins and B3GNT2 as drivers of cancer resistance to T cell-mediated cytotoxicity