Omics · study · 2026
CReP-mediated control of eIF2a phosphorylation is a central node in high-risk medulloblastoma [D458]
Listed in NCBI GEO
Medulloblastoma (MB) is the most common malignant pediatric brain tumor.
Description
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.
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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.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE290nnn/GSE290626 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE290626 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1229436 ncbi.nlm.nih.gov/bioproject/PRJNA1229436 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE290626 | 10 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:cancer | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[disease].local:disease:disease | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |