PXD031532 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-02-09 05:19:58 | ID requested | |
⏵ 1 | 2022-02-09 05:48:21 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: B3GNT2, melanoma, co-IP, shotgun proteomics |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD031532
- Label: PRIDE project
- Name: CRISPR activation screen identifies BCL-2 proteins and B3GNT2 as drivers of cancer resistance to T cell-mediated cytotoxicity