GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE328nnn/GSE328098/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE328098GEOGSEfalse3'UTR-directed, kinase proximal mRNA decay inhibits C/EBP phosphorylation/activation to suppress senescence in tumor cellsC/EBPβ regulates oncogene-induced senescence (OIS) and the SASP through its post-translational activation by the effector kinases ERK1/2 and CK2. 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. 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.2026/04/29GSE328098GSM9672370GSM9672371GSM9672372GSM9672365GSM9672366GSM9672367GSM9672368GSM967236934290328098Mus musculus