PXD041138-2

PXD041138 is an original dataset announced via ProteomeXchange.

Title	Systematic identification of anticancer drug targets reveals a nucleus-to-mitochondria ROS sensing pathway
Description	Multiple anticancer drugs have been proposed to cause cell death, in part, by increasing the steady-state levels of cellular reactive oxygen species (ROS). However, for most of these drugs exactly how the resultant ROS function and are sensed is poorly understood. It remains unclear which proteins the ROS modify and their roles in drug sensitivity/resistance. To answer these questions, we examined 11 anticancer drugs with an integrated proteogenomic approach identifying many unique targets but also shared ones–including ribosomal components, suggesting common mechanisms by which drugs regulate translation. We focus on CHK1 which we find is a nuclear H2O2 sensor that launches a cellular program to dampen ROS. CHK1 phosphorylates the mitochondrial-DNA binding protein SSBP1 to prevent its mitochondrial localization, which in turn decreases nuclear H2O2. Our results reveal a druggable nucleus-to-mitochondria ROS sensing pathway–required to resolve nuclear H2O2 accumulation and mediate resistance to platinum-based agents in ovarian cancers.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:45:16.073.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	JUNBING ZHANG
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	biotinylated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-27 16:35:24	ID requested
1	2024-06-15 23:10:28	announced
⏵ 2	2024-10-22 06:45:17	announced	2024-10-22: Updated project metadata.

10.1016/j.cell.2023.04.026;

Zhang J, Simpson CM, Berner J, Chong HB, Fang J, Ordulu Z, Weiss-Sadan T, Possemato AP, Harry S, Takahashi M, Yang TY, Richter M, Patel H, Smith AE, Carlin AD, Hubertus de Groot AF, Wolf K, Shi L, Wei TY, D, ü, rr BR, Chen NJ, Vornb, ä, umen T, Wichmann NO, Mahamdeh MS, Pooladanda V, Matoba Y, Kumar S, Kim E, Bouberhan S, Oliva E, Rueda BR, Soberman RJ, Bardeesy N, Liau BB, Lawrence M, Stokes MP, Beausoleil SA, Bar-Peled L, Systematic identification of anticancer drug targets reveals a nucleus-to-mitochondria ROS-sensing pathway. Cell, 186(11):2361-2379.e25(2023) [pubmed]

submitter keyword: Chermoresistance

Redox Signaling,ROS

chemical proteomics

Organelle Signaling

Chemotherapy

Liron Bar-Peled
contact affiliation	Center for Cancer Research, Massachusetts General Hospital, Boston MA, USA;Department of Chemistry and Chemical Biology, Harvard University, Cambridge MA, USA.
contact email	lbar-peled@mgh.harvard.edu
lab head
JUNBING ZHANG
contact affiliation	Massachusetts General Hospital
contact email	zhangjunbing@hotmail.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/2024/06/PXD041138

PRIDE project URI

• PRIDE
  1. PXD041138
     1. Label: PRIDE project
     2. Name: Systematic identification of anticancer drug targets reveals a nucleus-to-mitochondria ROS sensing pathway