PXD009290

PXD009290 is an original dataset announced via ProteomeXchange.

Title	Interruption of p53-MDM2 Interaction by Nutlin-3a in Human Lymphoma Cell Models Initiates a Cell-Dependent Global Effect on Transcriptome and Proteome Level
Description	In most lymphomas, p53 signaling pathway is inactivated by various mechanisms independent to p53 gene mutations or deletions. In many cases, p53 function is largely regulated by alterations in the protein abundance levels by the action of E3 ubiquitin-protein ligase MDM2, targeting p53 to proteasome-mediated degradation. In the present study, an integrating transcriptomics and pro-teomics analysis was employed to investigate the effect of p53 activation by a small-molecule MDM2-antagonist, nutlin 3a, on three lymphoma cell models following p53 activation. Our analy-sis revealed a system-wide nutlin 3a-associated effect in all examined lymphoma types, identifying in total of 4037 differentially affected proteins involved in a plethora of pathways, with significant heterogeneity among lymphomas. Our findings include known p53-targets and novel p53 activa-tion effects, involving transcription, translation, or degradation of protein components of path-ways, such as a decrease in key members of PI3K/mTOR pathway, heat-shock response, and gly-colysis, and an increase in key members of oxidative phoshosphorylation, autophagy and mito-chondrial translation. Combined inhibition of HSP90 or PI3K/mTOR pathway with nutlin 3a-mediated p53-activation enhanced the apoptotic effects suggesting a promising strategy against human lymphomas. Integrated omic profiling after p53 activation offered novel insights on the regulatory role specific proteins and pathways may have in lymphomagenesis.
HostingRepository	PRIDE
AnnounceDate	2024-10-07
AnnouncementXML	Submission_2024-10-07_13:28:56.768.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Michalis Aivaliotis
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	Bruker Daltonics SERVA-ICPL(TM) quantification chemistry, light form - site K; monohydroxylated residue; acetylated residue; Bruker Daltonics SERVA-ICPL(TM) quantification chemistry, heavy form - site K; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion; LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2018-03-22 02:03:29	ID requested
⏵ 1	2024-10-07 13:28:57	announced

Dataset with its publication pending

curator keyword: Biomedical

submitter keyword: proteomics,lymphoma, MDM2, apoptosis, transcriptomics, systems biology, nutlin 3a, p53

Michalis Aivaliotis
contact affiliation	Proteomics Facility, Institute at Molecular Biology and Biotechnology, FORTH, Heraklion, Crete, Greece, Laboratory of Biological Chemistry, Medical School, Aristotle University of Thessaloniki, Greece, Functional Proteomics and Systems Biology (FunPATh), Center for Interdisciplinary Research and Innovation (CIRI-AUTH), 54124 Thessaloniki, Greece
contact email	aivaliot@imbb.forth.gr
lab head
Michalis Aivaliotis
contact affiliation	IMBB-FORTH/AUTH
contact email	aivaliot@imbb.forth.gr
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/2023/07/PXD009290

PRIDE project URI

• PRIDE
  1. PXD009290
     1. Label: PRIDE project
     2. Name: Interruption of p53-MDM2 Interaction by Nutlin-3a in Human Lymphoma Cell Models Initiates a Cell-Dependent Global Effect on Transcriptome and Proteome Level