← BioTransfer GEO Dataset Finder
GEO series

Mis-splicing Drives Loss of Function of p53E224D Point Mutation

GSE239745 Homo sapiens (human) RNA-seq (gene expression) 15 samples Submitted 2024/07/28 Platform GPL24247Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 15 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Homo sapiens (human)
Samples
15 samples: 5 conditions, mostly in triplicateGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Summary (written by the submitters)
Background: Tp53 is the most commonly mutated gene in cancer. Canonical Tp53 DNA damage response pathways are well characterized and classically thought to underlie the tumor suppressive effect of Tp53. Challenging this dogma, mouse models have revealed that p53 driven apoptosis and cell cycle arrest are dispensable for tumor suppression.
Read the full summary ↓
Here, we investigated the inverse context of a p53 mutation predicted to drive expression of canonical targets, but is detected in human cancer. Methods: We established a novel mouse model with a single base pair mutation (GAG>GAC, p53E221D) in the DNA-Binding domain that has wild-type function in screening assays, but is paradoxically found in human cancer in Li Fraumeni syndrome. Using mouse p53 E221D and the the analogous human p53E224D mutant, we evaluated expression, transcriptional activation, and tumor suppression in vitro and in vivo. Results: Expression of human p53E224D from cDNA translated to a fully functional p53 protein. However, p53 E221D/E221D RNA transcribed from the endogenous locus is mis-spliced resulting in nonsense mediated decay. Moreover, fibroblasts derived from p53 E221D/E221D mice do not express a detectable protein product. Mice homozygous for p53 E221D exhibited increased tumor penetrance and decreased life expectancy compared to p53 WT animals. Conclusions: Mouse p53 E221D and human p53 E224D mutations lead to splice variation and a biologically relevant p53 loss of function in vitro and in vivo.
This dataset
Open GSE239745 in finder → Find more RNA-seq datasets →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE239745_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1000901 and SRA study SRP452492. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
5 conditions, mostly in triplicate
MEFS, E221D, ×3 MEFS, Wild-Type, biorep2, ×3 NCI-H716, ×3 HCT116, ×3 MEFS, Wild-Type, bioRep1, ×2 MEFS, Wild-Type, bioRep1 , ×1

Supports a between-group comparison across 14 samples.

How we read this: 5 replicated groups read from 15 sample titles; they account for 14 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
Datasets on a similar topic

Search all RNA-seq datasets in GEO →

Share this dataset

Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.