PXD047840

PXD047840 is an original dataset announced via ProteomeXchange.

Title	DrugMap: A quantitative pan-cancer analysis of cysteine ligandability
Description	Cysteine-focused chemical proteomic platforms have accelerated the clinical development of covalent inhibitors of a wide-range of targets in cancer. However, how different oncogenic contexts influence cysteine targeting remains unknown. To address this question, we have developed DrugMap, an atlas of cysteine ligandability compiled across 416 cancer cell lines. We unexpectedly find that cysteine ligandability varies across cancer cell lines, and we attribute this to differences in cellular redox states, protein conformational changes, and genetic mutations. Leveraging these findings, we identify actionable cysteines in NFκB1 and SOX10 and develop corresponding covalent ligands that block the activity of these transcription factors. We demonstrate that the NFkB1 probe blocks DNA binding, whereas the SOX10 ligand increases SOX10-SOX10 interactions and disrupts melanoma transcriptional signaling. Our findings reveal heterogeneity in cysteine ligandability across cancers, pinpoint cell-intrinsic features driving cysteine targeting,and illustrate the use of covalent probes to disrupt oncogenic transcription factor activity
HostingRepository	PRIDE
AnnounceDate	2024-04-23
AnnouncementXML	Submission_2024-04-23_14:14:37.904.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	liron bar-peled
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-14 14:33:25	ID requested
⏵ 1	2024-04-23 14:14:38	announced

10.1016/J.CELL.2024.03.027;

submitter keyword: cysteine ligandability,quantitative proteomics, LC-MS/MS

Bar-peled Liron
contact affiliation	MGH Cancer Center/Harvard Medical School
contact email	lbar-peled@mgh.harvard.edu
lab head
liron bar-peled
contact affiliation	MGH/HMS
contact email	lbar-peled@mgh.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/2024/04/PXD047840

PRIDE project URI

• PRIDE
  1. PXD047840
     1. Label: PRIDE project
     2. Name: DrugMap: A quantitative pan-cancer analysis of cysteine ligandability