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Ubiquitin specific peptidase 7 promotes TP53 mutant malignancy by deubiquitinating and stabilizing DDR1

GSE301195 Homo sapiens (human) RNA-seq (gene expression) 60 samples Submitted 2025/09/03 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 60 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
60 samples: 60 samples, each with a distinct title — no replicated groupsGroups 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.
Paper
Ubiquitin-specific protease 7-mediated stabilization of discoidin domain receptor 1 drives progression of TP53-Mutant cancersThe Journal of biological chemistry · 2025
Summary (written by the submitters)
Receptor tyrosine kinase DDR1 (Discoidin Domain Receptor 1) interacts with the extracellular matrix (ECM) to promote tumor cell proliferation through its intracellular kinase activity, while its extracellular non-enzymatic domain creates a physical barrier for immune evasion. Although DDR1 inhibitors and antibodies have been developed, targeting DDR1 kinase activity alone cannot fully block the biological effects mediated by its scaffold function.
Read the full summary ↓
Therefore, developing DDR1 degraders presents a potentially more effective therapeutic strategy. Through screening a proprietary small-molecule ubiquitination library, we identified NSC632839, which significantly induces DDR1 protein degradation. Mechanistically, chemical proteomics and genetic studies demonstrated that NSC632839 functions by inhibiting USP7, which interacts with, stabilizes, and deubiquitinates DDR1, preventing its proteasomal degradation. Importantly, we observed that TP53 loss or mutation in tumor cells and clinical samples markedly upregulates DDR1 expression, thereby enhancing its interaction with USP7. Treatment with NSC632839 restores TP53 expression, resulting in a significant reduction in DDR1 levels. In various preclinical models, targeting USP7 with NSC632839 effectively eliminates tumor cells, offering a promising therapeutic strategy to overcome tumor relapse driven by TP53 mutations, both in vitro and in vivo. This study highlights the potential of DDR1 degradation via USP7 inhibition as a novel approach to treat TP53 mutation-enriched tumors.
Published in
Ubiquitin-specific protease 7-mediated stabilization of discoidin domain receptor 1 drives progression of TP53-Mutant cancers
Xue Y, Xiu B, Yang M et al. · The Journal of biological chemistry 2025 · PMID 40713963 · doi:10.1016/j.jbc.2025.110515
This dataset
Open GSE301195 in finder → Find more human 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 GSE301195_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 PRJNA1284252 and SRA study SRP596082. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40713963) ↗
Study design
60 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 60 sample titles: 60 distinct titles with little repetition. 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

+ 20 more — browse all 60 samples with per-sample file links →

Datasets on a similar topic

Search all human RNA-seq datasets in GEO →

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