PXD077318-1

PXD077318 is an original dataset announced via ProteomeXchange.

Title	CReP-mediated control of eIF2a phosphorylation is a critical node in MYC-driven medulloblastoma
Description	Medulloblastoma (MB) is the most common malignant pediatric brain tumor. The MYC-amplified group 3 (G3) MB represents a high-risk disease lacking effective therapies. A genetic screen identified the endoplasmic reticulum chaperone HSPA5 (BiP/GRP78) as a critical dependency in G3 MB. Its silencing induces apoptosis and suppresses tumor growth, with strong activation of the unfolded protein response (UPR). The UPR includes three branches, including the PERK–eIF2α axis, which transiently reduces global protein synthesis while enabling selective translation of stress-responsive factors such as ATF4. We show that G3 MB requires sustained eIF2α activity for survival. Its inhibition triggers cell death through ATF4-dependent and -independent transcriptional programs and translational reprogramming that deplete essential proteins and promote accumulation of detrimental factors. The eIF2α phosphatase PPP1R15B (CReP) maintains basal eIF2α activity and prevents apoptosis. These findings identify the eIF2α axis and its regulators as a crucial node and a targetable vulnerability in G3 MB.
HostingRepository	PRIDE
AnnounceDate	2026-07-21
AnnouncementXML	Submission_2026-07-21_03:55:37.185.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Vanessa Masson
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2026-04-17 09:50:44	ID requested
⏵ 1	2026-07-21 03:55:37	announced

Dataset with its publication pending

submitter keyword: None

Damarys Loew
contact affiliation	Head of the Curie Institute Mass Spectrometry Platform
contact email	damarys.loew@curie.fr
lab head
Vanessa Masson
contact affiliation	Institut Curie - Centre de Recherche
contact email	vanessa.masson@curie.fr
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/2026/07/PXD077318

PRIDE project URI

• PRIDE
  1. PXD077318
     1. Label: PRIDE project
     2. Name: CReP-mediated control of eIF2a phosphorylation is a critical node in MYC-driven medulloblastoma