PXD029357

PXD029357 is an original dataset announced via ProteomeXchange.

Title	Monitoring Changes in the Levels of Newly Synthesized Proteins in Response to Nutlin-3 Treatment.
Description	Developing robust approaches for discovering protein-protein interactions remains a fundamental challenge in the life sciences. As an emerging view of protein-protein interactions in higher eukaryotes is that they are driven by a vast diversity of linear peptide motifs that drive combinatorial specificity in signal transduction. We focus on the E3 ubiquitin ligase component (MDM2) which plays a crucial role in inhibiting p53 and acting as an allosteric component of a multi-enzyme reaction in the ubiquitin transfer cascade that binds target proteins via a linear peptide-motif. Drugs targeting MDM2’s hydrophobic pocket that mimic peptide activate p53, which was described that it has unrestrained function can lead to massive cell death. However, these agents act allosterically and have agonist effects on MDM2’s protein interaction landscape. Dominant p53-independent MDM2-drug responsive binding proteins have not been stratified. As it is known that MDM2 can change its degradation rate as a function of cell density, we probed the impact of Nutlin-3 on protein synthesis rates using pulse-SILAC. Mass-spectrometry-based proteomics is used for giving detailed qualitative and quantitative information as well as a comprehensive view of protein-protein interactions. The data demonstrate that at differing cell densities different proteins dominate the synthesis landscape in an MDM2-dependent manner and further confirm that the cell state can in turn impact on the MDM2 signaling landscape. This methodology forms a blueprint for biomarker discovery that can identify re-arrangements of MDM2 proteome complexes in drug treated cells. Broader implication highlight tools that can be used to study allosteric regulation of any protein factor.
HostingRepository	PRIDE
AnnounceDate	2025-03-03
AnnouncementXML	Submission_2025-03-03_07:04:25.785.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Lenka Hernychova
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	6x(13)C labeled residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2021-10-26 01:24:51	ID requested
1	2025-02-28 05:46:06	announced
⏵ 2	2025-03-03 07:04:26	announced	2025-03-03: Updated project metadata.

10.1002/PMIC.202400333;

submitter keyword: P53, Signal transduction, pulse-SILAC, MDM2, biomarker discovery,LC-MSMS

Atef Mannaa
contact affiliation	Borg AlArab Higher Institute of Engineering and Technology, New Borg AlArab City, Alexandria, Egypt
contact email	atef.mannaa8@gmail.com
lab head
Lenka Hernychova
contact affiliation	Masaryk Memorial Cancer Institutre, Zluty kopec 7, Brno 656 53, Czech Republic
contact email	lenka.hernychova@mou.cz
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/2025/02/PXD029357

PRIDE project URI

• PRIDE
  1. PXD029357
     1. Label: PRIDE project
     2. Name: Monitoring Changes in the Levels of Newly Synthesized Proteins in Response to Nutlin-3 Treatment.