PXD047240-1

PXD047240 is an original dataset announced via ProteomeXchange.

Title	Modeling cooperative tumor suppression in the p53 target gene network with in vivo genetic screens and multi-omics
Description	The tumor suppressor TP53 is the most frequently mutated gene in human cancer. TP53 encodes a transcriptional activator that induces numerous downstream target genes, but those genes critical for tumor suppression remain elusive. To shed light on the downstream target genes important for tumor suppression, we developed a sensitive and unbiased in vivo CRISPR/Cas9 screening platform to comprehensively map key downstream effectors of p53 in tumor suppression, an essential goal for revealing pathways that could be ultimately therapeutically targeted in p53-deficient tumors. These screens consistently revealed Zmat3 and Cdkn1a as the top-scoring tumor suppressors and demonstrated their capacity to cooperate in tumor suppression. To understand the genetic programs and cellular phenotypes regulated by Zmat3 and Cdkn1a, we used shotgun proteomics to assess differences in protein expression between wild-type, Zmat3 KO, Zmat3 + Cdkn1a KO, and p53 KO E1A;HrasG12V murine embryonic fibroblasts. Functional annotation revealed that various cellular programs including cell division, extracellular signaling and signal transduction, viral response, and ribosome biogenesis become dysregulated in cell lines with alterations to the p53 pathway compared to the wild-type cell lines. These data suggest cellular processes and signaling pathways that provide clues to understanding p53-mediated tumor suppression and for the development of treatments for p53 deficient tumors.
HostingRepository	PRIDE
AnnounceDate	2026-07-17
AnnouncementXML	Submission_2026-07-16_20:16:29.211.xml
DigitalObjectIdentifier	https://doi.org/10.6019/PXD047240
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Janos Demeter
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	phosphorylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-25 15:51:41	ID requested
⏵ 1	2026-07-16 20:16:31	announced

10.1101/2024.09.17.612743;

10.6019/PXD047240;

Boutelle AM, Mabene AR, Yao D, Xu H, Wang M, Tang YJ, Lopez SS, Sinha S, Demeter J, Cheng R, Benard BA, Valente LJ, Drainas AP, Fischer M, Majeti R, Petrov DA, Jackson PK, Yang F, Winslow MM, Bassik MC, Attardi LD, Integrative multiomic approaches reveal ZMAT3 and p21 as conserved hubs in the p53 tumor suppression network. bioRxiv, ():(2024) [pubmed]

submitter keyword: mouse, embryonic fibroblast, p53

Peter K Jackson
contact affiliation	Peter K. Jackson, Baxter Laboratory for Stem Cell Biology Department of Microbiology & Immunology Stanford University School of Medicine 269 Campus Drive Stanford, CA 94305-5175, USA
contact email	pjackson@stanford.edu
lab head
Janos Demeter
contact affiliation	Stanford University
contact email	jdemeter@stanford.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/2026/07/PXD047240

PRIDE project URI

• PRIDE
  1. PXD047240
     1. Label: PRIDE project
     2. Name: Modeling cooperative tumor suppression in the p53 target gene network with in vivo genetic screens and multi-omics