PXD045157

PXD045157 is an original dataset announced via ProteomeXchange.

Title	Ezrin defines TSC1 activation at endosomal compartment through EGFR-AKT signaling
Description	Endosomes have emerged as major signaling hubs, in which different internalized ligand-receptor complexes are integrated and outcome of signaling pathways are organized to regulate the strength and specificity of the cellular signal transduction events. Ezrin, a major membrane-actin linker assembling and coordinating macromolecular signaling complexes at the membranes, has recently emerged as important regulator of lysosomal function. Here, we reported that Ezrin binds Epidermal Growth Factor Receptor (EGFR) and controls its dimerization, activation and endosomal internalization upon EGF stimuli. Endosomal-localized EGFR/Ezrin complex interacts and triggers the inhibition of Tuberous Sclerosis Complex (TSC) through activation of AKT signaling pathway. AKT phosphorylates and inhibits its substrate TSC at endosomal compartment. Depletion or inactivation of Ezrin leads to inhibition of EGFR endocytosis and signaling, thereby relieving TSC inhibition by AKT and triggering translocation of TSC to lysosomes, where it suppresses mTORC1 signaling. Our findings identify the molecular machinery that controls the spatiotemporal activation of autophagy by Ezrin and establish the central role of endosomal signaling in the differential regulation of TSC by EGFR signaling.
HostingRepository	PRIDE
AnnounceDate	2025-01-31
AnnouncementXML	Submission_2025-01-31_00:42:36.791.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Rossella De Cegli
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-06 07:52:58	ID requested
⏵ 1	2025-01-31 00:42:37	announced

10.7554/ELIFE.98523.2;

ProteomeXchange project tag: Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

submitter keyword: Ezrin, TSC1, EGFR

Ivan Conte
contact affiliation	Department of Biology, University of Naples Federico II, Strada Vicinale Cupa Cintia, 21, Naples 80126 Italy
contact email	ivan.conte@unina.it
lab head
Rossella De Cegli
contact affiliation	Telethon Institute of Genetics and Medicine (TIGEM)
contact email	decegli@tigem.it
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/2025/01/PXD045157

PRIDE project URI

• PRIDE
  1. PXD045157
     1. Label: PRIDE project
     2. Name: Ezrin defines TSC1 activation at endosomal compartment through EGFR-AKT signaling