PXD060549-1

PXD060549 is an original dataset announced via ProteomeXchange.

Title	Unveiling the impact of AKT1 pathogenic variants in Juvenile Granulosa Cell Tumors Using a Drosophila model
Description	Juvenile-type granulosa cell tumors (JGCTs) manifest during the prepubertal period as precocious pseudo-puberty and/or dysmenorrhea. We have previously identified pathogenic variants in AKT1 in JGCTs. The current study aims to understand how these variants affect cellular function at the phenotypic and molecular levels. To do this, we created transgenic Drosophila models expressing wild-type (WT) AKT1 and four pathogenic variants, under the control of tissue-specific promoters. Drosophila wings were used to assess the effects of mutated AKT1 on cell division and growth by measuring trichome density. Wings expressing mutated AKT1 showed an increased surface area and a reduced trichome density, indicating the presence of probably larger cells. In ovarian follicular cells, the AKT1 WT localized mainly in the cytoplasm, while the mutated variants are found in the plasma membrane. This localization led to various morphological abnormalities and a significant increase in cell size. Mass spectrometry (MS) revealed a number of differentially expressed proteins (DEPs) and phospho-peptides pointing to significant changes in pathways such as glycolysis and Rho GTPases signaling in response to AKT1 mutation. At the transcriptional level, as expected for activating oncogenic mutations, we found a clear gain-of-function of the mutated forms for a gene subset. However, we also found that a series of genes up-regulated by WT AKT1 were less well activated by the mutated forms. This suggests the existence of a potential loss-of-function of mutated AKT1 on the transcriptional regulation of this specific gene subset, pointing to an unanticipated mechanistic complexity. The analysis of the network of interactions involving DEPs, differentially phosphorylated proteins and transcription factors, probably mediating the aforementioned transcriptional alterations, highlights the central role of AKT1 as a cancer driver. Our results taken altogether underscore the utility of Drosophila as a model to understanding the biological relevance of AKT mutations in cancer.
HostingRepository	PRIDE
AnnounceDate	2026-01-12
AnnouncementXML	Submission_2026-01-11_17:36:09.653.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Guillaume CHEVREUX
SpeciesList	scientific name: Drosophila melanogaster (Fruit fly); NCBI TaxID: NEWT:7227;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue
Instrument	Orbitrap Fusion; Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-06 04:49:44	ID requested
⏵ 1	2026-01-11 17:36:10	announced

10.1016/j.mcpro.2025.101466;

Veitia RA, Herman L, Legois B, Claret S, Zider A, Todeschini AL, Deciphering the Impact of AKT1 Pathogenic Variants in Juvenile Granulosa Cell Tumors Using a Drosophila Model. Mol Cell Proteomics, 24(12):101466(2025) [pubmed]

submitter keyword: fly, Juvenile Granulosa cell tumors,AKT1, ovary

Anne-Laure, Todeschini
contact affiliation	Université Paris Cité, CNRS, Institut Jacques Monod, F-75013 Paris, France.
contact email	anne-laure.todeschini@ijm.fr
lab head
Guillaume CHEVREUX
contact affiliation	Institut Jacques Monod, CNRS UMR7592
contact email	guillaume.chevreux@ijm.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD060549
     1. Label: PRIDE project
     2. Name: Unveiling the impact of AKT1 pathogenic variants in Juvenile Granulosa Cell Tumors Using a Drosophila model