PXD056704 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Covalent Targeting of Splicing in T Cells. |
Description | Despite significant interest in therapeutic targeting of splicing, few chemical probes are available for the proteins involved in splicing. Here, we show that elaborated stereoisomeric acrylamide EV96 and its analogues lead to a selective T cell state-dependent loss of interleukin 2-inducible T cell kinase (ITK) by targeting one of the core splicing factors SF3B1. Mechanistic investigations suggest that the state-dependency stems from a combination of differential protein turnover rates and extensive ITK mRNA alternative splicing. We further introduce the most comprehensive list to date of proteins involved in splicing and leverage cysteine- and protein-directed activity-based protein profiling with electrophilic scout fragments to demonstrate covalent ligandability for many classes of splicing factors and splicing regulators in T cells. Taken together, our findings show how chemical perturbation of splicing can lead to immune state-dependent changes in protein expression and provide evidence for the broad potential to target splicing factors with covalent chemistry. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-21_18:14:07.607.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Ekaterina Vinogradova |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | TMT6plex-126 reporter+balance reagent acylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Eclipse |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-10-10 16:47:36 | ID requested | |
⏵ 1 | 2024-10-21 18:14:08 | announced | |
Publication List
Scott KA, Kojima H, Ropek N, Warren CD, Zhang TL, Hogg SJ, Webster C, Zhang X, Rahman J, Melillo B, Cravatt BF, Lyu J, Abdel-Wahab O, Vinogradova EV, Covalent Targeting of Splicing in T Cells. bioRxiv, ():(2023) [pubmed] |
10.1101/2023.12.18.572199; |
Keyword List
submitter keyword: SF3B1, splicing,chemical proteomics, T cells |
Contact List
Ekaterina Viktorovna Vinogradova |
contact affiliation | The Rockefeller University, Laboratory of Chemical Immunology and Proteomics |
contact email | vinograd@rockefeller.edu |
lab head | |
Ekaterina Vinogradova |
contact affiliation | The Rockefeller University |
contact email | vinograd@rockefeller.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD056704
- Label: PRIDE project
- Name: Covalent Targeting of Splicing in T Cells.