PXD051502

PXD051502 is an original dataset announced via ProteomeXchange.

Title	Relocalizing transcriptional kinases to activate apoptosis_Proteomics Data
Description	Kinases are critical regulators of cellular function that are commonly implicated in the mechanisms underlying disease. Most drugs that target kinases are molecules that inhibit their catalytic activity, but here we used chemically induced proximity to convert kinase inhibitors into activators of therapeutic genes. We synthesized bivalent molecules that link ligands of the transcription factor B cell lymphoma 6 (BCL6) to inhibitors of cyclin-dependent kinases (CDKs). These molecules relocalized CDK9 to BCL6-bound DNA and directed phosphorylation of RNA polymerase II. The resulting expression of pro-apoptotic, BCL6-target genes caused killing of diffuse large B cell lymphoma cells and specific ablation of the BCL6-regulated germinal center response. Genomics and proteomics corroborated a gain-of-function mechanism in which global kinase activity was not inhibited but rather redirected. Thus, kinase inhibitors can be used to context-specifically activate transcription. This PRIDE entry contains the raw proteomics data and DIA-NN search output.
HostingRepository	PRIDE
AnnounceDate	2024-12-20
AnnouncementXML	Submission_2024-12-20_11:35:31.894.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Brendan Dwyer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	timsTOF HT

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-16 13:09:28	ID requested
⏵ 1	2024-12-20 11:35:33	announced

10.1101/2023.10.23.563687;

Sarott R, Gourisankar S, Karim B, Nettles S, Yang H, Dwyer BG, Simanauskaite JM, Tse J, Abuzaid H, Krokhotin A, Zhang T, Hinshaw SM, Green MR, Crabtree GR, Gray NS, Borrowing Transcriptional Kinases to Activate Apoptosis. bioRxiv, ():(2023) [pubmed]

10.1126/science.adl5361;

Sarott RC, Gourisankar S, Karim B, Nettles S, Yang H, Dwyer BG, Simanauskaite JM, Tse J, Abuzaid H, Krokhotin A, Zhang T, Hinshaw SM, Green MR, Crabtree GR, Gray NS, Relocalizing transcriptional kinases to activate apoptosis. Science, 386(6717):eadl5361(2024) [pubmed]

submitter keyword: cancer, lymphoma, transcription,Kinase

Nathanael S.
contact affiliation	Professor of Chemical and Systems Biology at Stanford
contact email	nsgray01@stanford.edu
lab head
Brendan Dwyer
contact affiliation	Stanford University
contact email	dwyermrbrendan@gmail.com
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/2024/12/PXD051502

PRIDE project URI

• PRIDE
  1. PXD051502
     1. Label: PRIDE project
     2. Name: Relocalizing transcriptional kinases to activate apoptosis_Proteomics Data