Omics · study · 2026
The Deubiquitinating Enzyme Otub2 Modulates Pancreatic Beta-Cells Function and Survival
Listed in NCBI GEO
We have previously shown that otubain 2 (OTUB2), a deubiquitinating enzyme, inhibits caspase-3/7 activity in primary human islets; promotes insulin secretion and inhibits cytokine-induced nuclear factor-κB (NFκB) activity.
Description
In the present work we show that overexpression of Otub2 in MIN6 cells inhibits NFκB activity and the expression of its target genes MCP-1 and iNOS. Consequently, both the basal and the cytokine-induced apoptosis of cultured MIN6 cells and dispersed human islets were inhibited.
Overexpression of Otub2 in MIN6 cells increase the mRNA levels of NKx6.1 and Glut2 and concomitantly increased glucose-stimulated insulin secretion (GSIS) (by 2-3-fold). The beneficial effects of Otub2 on β-cell function was demonstrated by the phenotype of Otub2-/+ and Otub2-/- mice, which manifested impaired glucose tolerance and increased expression of NFkB target genes (e.g. IP-10, MCP-1 and IL-1b). RNAseq analysis of pancreata derived from OTUB2 KO mice revealed reduced expression of genes that down regulate K+ transporters (e.g. Ank2, Cacna1a and Kcnab1) combined with an increase in oxidative phosphorylation related genes.
Read the rest (2 more)
Given that closure of K+ channels is crucial for insulin secretion, these results could account, at least in part, for the impaired GSIS in the OTUB2 KO mice. Indeed, mass-spectrometry analysis of proteins co-immunoprecipitated with Otub2 revealed the voltage-gated potassium channel subunit Kv9.3 as a major Otub2 binding-partner. Additional binding partners included the Peg3 and Camk2d proteins, which promote NFκB signaling and β-cell death.
Hence, by deubiquitinating proteins in complexes that contain Peg3 and Camk2d, Otub2 might inhibit propagation of NFκB signaling and β-cell apoptosis. Collectively our findings implicate Otub2 as a key regulator of b cell function, mainly affecting NFkB signaling and the K+ channels that regulate insulin secretion.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE285nnn/GSE285973 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE285973 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1207084 ncbi.nlm.nih.gov/bioproject/PRJNA1207084 ↗
project · from NCBI GEO
- PubMed 41914276 pubmed.ncbi.nlm.nih.gov/41914276 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- RNA sequencing 65%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE285973 | 14 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| 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: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 |