GEO series

Targeting Mannosylation of Nicastrin N-glycans Attenuates γ-Secretase Activity and Notch-dependent Leukemia Progression

GSE320527 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2026/07/06 Platform GPL34284

At a glance

RNA-seq (gene expression) · human · 12 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: 12 samples: 3 × WT, vs 3 × DOCK2 KO, vs 3 × dbz treatment, vs 3 × kifunensine treatment,Groups 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)

γ-Secretase is a transmembrane protease complex that cleaves multiple type I transmembrane proteins, including amyloid precursor protein and NOTCH. Although numerous γ-secretase inhibitors and modulators targeting Notch-dependent cancers have been developed in recent decades, their clinical translation has been hampered by low substrate specificity and on-target gut toxicity.

Read the full summary ↓

Using a proteomics-based screening approach, we identified dedicator of cytokinesis protein 2 (DOCK2) as an interactor of the γ-secretase subunit Nicastrin (NCSTN). We further demonstrate that DOCK2 regulates mannosylation of NCSTN N-glycans, which in turn modulates γ-secretase activity toward NOTCH receptors. Both genetic depletion of DOCK2 and pharmacological inhibition of NCSTN mannosylation with Kifunensine attenuated Notch-dependent leukemia progression in vivo. Collectively, these findings uncover a regulatory mechanism underlying substrate-specific activation of γ-secretase and suggest a promising therapeutic strategy for Notch-related diseases.

This dataset

Open GSE320527 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 GSE320527_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 PRJNA1428773 and SRA study SRP679536. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

3 × WT, vs 3 × DOCK2 KO, vs 3 × dbz treatment, vs 3 × kifunensine treatment,

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 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

GSM9544990 WT, replicate1 WT,
GSM9544991 WT, replicate2 WT,
GSM9544992 WT, replicate3 WT,
GSM9544993 DOCK2 KO, replicate1 DOCK2 KO,
GSM9544994 DOCK2 KO, replicate2 DOCK2 KO,
GSM9544995 DOCK2 KO, replicate3 DOCK2 KO,
GSM9544996 dbz treatment, replicate1 dbz treatment,
GSM9544997 dbz treatment, replicate2 dbz treatment,
GSM9544998 dbz treatment, replicate3 dbz treatment,
GSM9544999 kifunensine treatment, replicate1 kifunensine treatment,
GSM9545000 kifunensine treatment, replicate2 kifunensine treatment,
GSM9545001 kifunensine treatment, replicate3 kifunensine treatment,

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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.