PXD056704

PXD056704 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-10 16:47:36	ID requested
⏵ 1	2024-10-21 18:14:08	announced

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;

submitter keyword: SF3B1, splicing,chemical proteomics, T cells

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

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/2024/10/PXD056704

PRIDE project URI

• PRIDE
  1. PXD056704
     1. Label: PRIDE project
     2. Name: Covalent Targeting of Splicing in T Cells.