Omics · study · 2026
3'UTR-directed, kinase proximal mRNA decay inhibits C/EBP phosphorylation/activation to suppress senescence in tumor cells
Listed in NCBI GEO
C/EBPβ regulates oncogene-induced senescence (OIS) and the SASP through its post-translational activation by the effector kinases ERK1/2 and CK2.
Description
However, in tumor cells, C/EBPb activity is suppressed by its 3'UTR. 3′UTR regulation of protein activity (UPA) requires a G/U-rich element (GRE) and its cognate binding protein, HuR. These components segregate CEBPB transcripts away from a perinuclear compartment harboring ERK1/2 and CK2 on signaling endosomes, preventing C/EBPβ from accessing its activating kinases.
We report here that the mRNA decay proteins Up-frameshift protein 1 (UPF1) and Staufen1/2 (STAU1/2) are also essential UPA factors. STAU1/2 and UPF1 overlap with CK2 on perinuclear endosomes where they promote localized CEBPB mRNA decay. UPF1 or STAU1/2 depletion in tumor cells increased CEBPB transcripts adjacent to CK2 foci, coinciding with C/EBPβ activation and senescence.
Read the rest (2 more)
The GRE and an adjacent STAU binding site both suppress C/EBPβ-mediated senescence, while a distinct 3'UTR region inhibits C/EBPβ’s SASP-inducing activity. KrasG12D-driven lung tumors in mice carrying a Cebpb GRE deletion rarely progressed to adenocarcinomas, demonstrating the importance of UPA for cancer malignancy in vivo. Immortalized GRED/D mouse embryonic fibroblasts (MEFs) also display enhanced OIS through up-regulation of the pro-senescent cytokine, S100a9, but not other SASPs.
Thus, kinase-proximal mRNA decay is a novel mechanism to inhibit C/EBPβ activity and facilitate senescence bypass in tumor cells. scRNA-seq was performed using WT and GRED/D lung tumor samples to deetermine the effect of the GRE deletion on tumor evolution through different stages.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE328nnn/GSE328098 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE328098 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1453915 ncbi.nlm.nih.gov/bioproject/PRJNA1453915 ↗
project · from NCBI GEO
- PubMed 42597915 pubmed.ncbi.nlm.nih.gov/42597915 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Cancer 75% · Single-cell RNA sequencing 65%
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE328098 | 15 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 (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[modality].local:modality:single-cell-rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[organism].NCBITaxon:10090 | 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 |