ArticleJournal of cellular and molecular medicine2020
USP15 promotes the apoptosis of degenerative nucleus pulposus cells by suppressing the PI3K/AKT signalling pathway.
Article in Journal of cellular and molecular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Ubiquitination in intervertebral disc degeneration: from mechanisms to potential therapeutic strategies.Journal of orthopaedic translation · 2026Review
- Integrated Molecular Docking and Network-Based Analysis Reveals Multitarget Interaction Patterns of Nutraceutical Compounds in Intervertebral Disc Degeneration.Biomedicines · 2026Article
- 'Nelfinavir sensitizes a clinically relevant chemo-radioresistant cervical cancerBiochemistry and biophysics reports · 2025Article
- USP41 plays carcinogenic roles in human cutaneous melanoma through PI3K/Akt signaling pathway.Archives of dermatological research · 2025Article
- Tissue engineering strategies for treating intervertebral disc degeneration.Frontiers in bioengineering and biotechnology · 2025Review
- LRP1 mitigates intervertebral disc degeneration by inhibiting endoplasmic reticulum stress through stabilizing the PPARγ.Journal of orthopaedic translation · 2025Article
- Deubiquitylating Enzymes in Cancer and Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- PLOD2 promotes colorectal cancer progression by stabilizing USP15 to activate the AKT/mTOR signaling pathway.Cancer science · 2023Article
- TSG-6 inhibits IL-1β-induced inflammatory responses and extracellular matrix degradation in nucleus pulposus cells by activating the PI3K/Akt signaling pathway.Journal of orthopaedic surgery and research · 2022Article
- USP15 regulates p66Shc stability associated with Drp1 activation in liver ischemia/reperfusion.Cell death & disease · 2022Article
- USP15 in Cancer and Other Diseases: From Diverse Functionsto Therapeutic Targets.Biomedicines · 2022Review
- Pro-apoptotic and anti-apoptotic regulation mediated by deubiquitinating enzymes.Cellular and molecular life sciences : CMLS · 2022Review
- Acute Myeloid Leukemia-Related Proteins Modified by Ubiquitin and Ubiquitin-like Proteins.International journal of molecular sciences · 2022Review
- Positive feedback regulation between USP15 and ERK2 inhibits osteoarthritis progression through TGF-β/SMAD2 signaling.Arthritis research & therapy · 2021Article
- Role of PI3K/AKT Signaling Pathway in Nucleus Pulposus Cells.BioMed research international · 2021Article
- USP15 promotes the apoptosis of degenerative nucleus pulposus cells by suppressing the PI3K/AKT signalling pathway.Journal of cellular and molecular medicine · 2020Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesDegenerative disc disease is characterized by an enhanced breakdown of its existing nucleus pulposus (NP) matrix due to the dysregulation of matrix enzymes and factors. Ubiquitin-specific protease 15 (USP15) is reported to be abnormal in certain human diseases. However, its role in NP degeneration remains unclear. Therefore, we aimed to explore the function of USP15 in degenerative NP cell specimens.
methodsWe induced gene silencing and overexpression of USP15 in degenerative NP cells using RNA interference (RNAi) and a lentiviral vector, respectively. qRT-PCR and Western blotting were used to determine gene and protein expression levels. Cell apoptosis was analysed via flow cytometry. Protein interaction was examined by performing a co-immunoprecipitation assay. Furthermore, the PI3K inhibitor LY294002 and agonist IGF-1 were used to investigate the link between USP15 and AKT in NP degeneration.
resultsWe found that USP15 was up-regulated in degenerative NP cells and that its overexpression accelerated the process of apoptosis. Moreover, USP15 expression levels negatively correlated with AKT phosphorylation in degenerative NP cells. Furthermore, targeting and silencing USP15 with miR-338-3p and studying its interaction with FK506-binding protein 5 (FKBP5) revealed enhancement of FKBP5 ubiquitination, indicating that USP15 is a component of the FKBP5/AKT signalling pathway in degenerative NP cells.
conclusionsOur results show that USP15 exacerbates NP degradation by deubiquitinating and stabilizing FKBP5. This in turn results in the suppression of AKT phosphorylation in degenerative NP cells. Therefore, our study provides insights into the understanding of USP15 function as a potential molecule in the network of NP degeneration.
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