PXD040668-1

PXD040668 is an original dataset announced via ProteomeXchange.

Title	ITK Degradation to Block T-cell Receptor Signaling and Overcome Therapeutic Resistance in T-Cell Lymphomas
Description	IL-2-inducible T cell kinase (ITK) is essential for T cell receptor (TCR) signaling and plays an integral role in T-cell proliferation and differentiation. Unlike the ITK homolog BTK, no inhibitors of ITK are currently FDA approved. In addition, recent studies have identified mutations within BTK that confer resistance to both covalent and non-covalent inhibitors. Here, as an alternative strategy, we report the development of BSJ-05-037, a potent and selective heterobifunctional degrader of ITK. BSJ-05-037 displayed enhanced anti-proliferative effects relative to its parent catalytic inhibitor, blocked the activation of NF-kB/GATA-3 signaling and increased the sensitivity of T cell lymphoma cells to cytotoxic chemotherapy both in vitro and in vivo. In summary, targeted degradation of ITK is a novel approach to modulate TCR signal strength that could have broad application for the investigation and treatment of T cell-mediated diseases.
HostingRepository	PRIDE
AnnounceDate	2023-05-29
AnnouncementXML	Submission_2023-05-29_15:11:01.661.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	EricFischer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-07 19:02:23	ID requested
⏵ 1	2023-05-29 15:11:02	announced
2	2023-11-14 09:00:36	announced	2023-11-14: Updated project metadata.

submitter keyword: lymphoma, cereblon, kinase, PROTAC, ubiquitin,degrader, ITK

EricFischer
contact affiliation	Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
contact email	eric_fischer@dfci.harvard.edu
lab head
EricFischer
contact affiliation	Dana-Farber Cancer Institute
contact email	eric_fischer@dfci.harvard.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/2023/05/PXD040668

PRIDE project URI

• PRIDE
  1. PXD040668
     1. Label: PRIDE project
     2. Name: ITK Degradation to Block T-cell Receptor Signaling and Overcome Therapeutic Resistance in T-Cell Lymphomas