PXD021188

PXD021188 is an original dataset announced via ProteomeXchange.

Title	Mutations in TRAF7 drive meningioma development by dysregulating proteostasis of the RAS-like GTPases
Description	Meningiomas are the most common primary brain tumors, where complete surgical resection is often challenging giving rise to recurrence. Mutations of the E3 ubiquitin ligase TRAF7 are found in one-fourth of meningioma patients and typically co-occur with mutations in either KLF4, AKT1, or PI3KCA. By creating an in vitro meningioma model derived from primary meningeal cells, we elucidated the cooperative interactions that conspire meningioma development. A multi-omics framework on meningeal cells revealed TRAF7-mediated rewiring of the proteome with the majority of protein expression being post‐transcriptionally‐regulated. Integrating TRAF7-driven ubiquitinome and proteome alterations and TRAF7 interactome highlight the role of TRAF7 in posttranslational regulation of the cytoskeleton organization. TRAF7 controls actin dynamics by acting as a proteostatic regulator of the RAS-related small GTPases. TRAF7 loss-of-function diminishes ubiquitination of RAS and CDC42, leading to the activation of the PAK and MAPK signaling pathways. Up-regulation of CDC42 signaling promotes anchorage-independent growth of meningeal cells. On the other hand, the RAS/MAPK pathway triggers the tumor suppressive activity of KLF4 that inhibits meningeal cell growth due to the activation of the Semaphorin pathway. Simultaneous loss of KLF4 and TRAF7 function enhances tumorigenic transformation of meningeal cells, functionally confirming their roles in meningioma development.
HostingRepository	PRIDE
AnnounceDate	2024-06-19
AnnouncementXML	Submission_2024-06-19_02:00:27.583.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Teresa Mendes Maia
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	ubiquitination signature dipeptidyl lysine; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-08-28 03:53:17	ID requested
⏵ 1	2024-06-19 02:00:27	announced

10.1158/0008-5472.CAN-20-3669;

submitter keyword: meningioma, cancer, multi-omics, actin cytoskeleton, RAS pathway, Semaphorin pathway, proteostasis

Anna Sablina
contact affiliation	VIB-KU Leuven Center for Cancer Biology, VIB, 3000 Leuven, Belgium
contact email	Anna.Sablina@vib-ugent.be
lab head
Teresa Mendes Maia
contact affiliation	VIB Proteomics Core
contact email	teresa.maia@vib-ugent.be
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD021188
     1. Label: PRIDE project
     2. Name: Mutations in TRAF7 drive meningioma development by dysregulating proteostasis of the RAS-like GTPases