PXD025056

PXD025056 is an original dataset announced via ProteomeXchange.

Title	Comparative proteomics identifies different metabolic pathways activated by p53 mutants G245S and R337H associated with Li-Fraumeni syndrome
Description	Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition disorder associated with germline mutations in the TP53 tumor suppressor gene. The p53 mutation spectrum associated with LFS is similar to that found in somatic tumors, with most of them, such as the G245S mutation, occurring in the DNA-binding domain of protein. However, in Brazil the most frequent p53 mutation associated with LFS, R337H, affects the oligomerization domain of p53. The goal of this study is to characterize the molecular pathways activated by p53 mutants G245S and R337H in cancer cells. The p53-null NCI-H1299 cell line was stably transfected with pCMV-Neo-Bam vectors to drive expression of the G245S and R337H p53 mutants and nuclear localization of mutant p53s was verified by western blot and immunocytochemistry. The molecular pathways activated by mutant p53s were characterized by cellular proteomics using DIA-based mass spectrometry. Cell assays confirmed the functional enrichment of oxidative phosphorylation and mitochondrial ATP synthesis proteins in cells expressing R337H p53 that may account for the increased aerobic respiration levels and higher mitochondrial activity. In contrast, glycolysis and angiogenesis were pathways upregulated in cells expressing G245S p53 which could be related to glucose- and L-glutamine-dependent proliferation, decreased aerobic respiration and higher capacity to form spheroids.
HostingRepository	PRIDE
AnnounceDate	2026-06-29
AnnouncementXML	Submission_2026-06-28_19:25:32.625.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Richard Wilson
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-03-29 02:45:16	ID requested
⏵ 1	2026-06-28 19:25:33	announced

10.1016/j.biochi.2022.03.003;

Meneghetti BV, Wilson R, Dias CK, Cadore NA, Klamt F, Zaha A, Ferreira HB, Monteiro KM, p53 mutants G245S and R337H associated with the Li-Fraumeni syndrome regulate distinct metabolic pathways. Biochimie, 198():141-154(2022) [pubmed]

submitter keyword: metabolism, oxidative phosphorylation, Li-Fraumeni Syndrome, R337H, respiration, cancer cells, G245S,TP53, glycolysis, mutation

Dr Richard Wilson
contact affiliation	Proteomics facility, Central Science Laboratory, University of Tasmania
contact email	richard.wilson@utas.edu.au
lab head
Richard Wilson
contact affiliation	University of Tasmania
contact email	richard.wilson@utas.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD025056
     1. Label: PRIDE project
     2. Name: Comparative proteomics identifies different metabolic pathways activated by p53 mutants G245S and R337H associated with Li-Fraumeni syndrome