ArticleCancer letters2022
NEDD4 degrades TUSC2 to promote glioblastoma progression.
Article in Cancer letters, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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The trial behind it
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Who cites it
9 citing papers in PubMed, 14 citations in OpenAlex.
- BCL-2 and BCL-xL in Cancer: Regulation, Function, and Therapeutic Targeting.International journal of molecular sciences · 2026Review
- Targeting the SYVN1-EGFR axis: a breakthrough strategy for TKI-resistant NSCLC.Cell death & disease · 2025Article
- Comprehensive analysis of the role of NEDD4 in pan-cancer and experimental verification of its role in KIRC progression.Discover oncology · 2025Article
- NEDD4 facilitates the progression of endometrial carcinoma by enhancing PAMR1 protein degradation through ubiquitination.Functional & integrative genomics · 2025Article
- Unveiling the Role of Protein Posttranslational Modifications in Glioma Prognosis.CNS neuroscience & therapeutics · 2025Article
- Immunohistochemical and molecular evaluation of TUSC2 expression in breast cancer.Molecular biology reports · 2024Article
- Lysine methylation promotes NFAT5 activation and determines temozolomide efficacy in glioblastoma.Nature communications · 2023Article
- Review
- Comprehensive Characterization of a Novel E3-Related Gene Signature With Implications in Prognosis and Immunotherapy of Low-Grade Gliomas.Frontiers in genetics · 2022Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
Whether tumor suppressor candidate 2 (TUSC2) plays an important role in glioblastoma (GBM) progression is largely unknown. Whether TUSC2 undergoes polyubiquitination is unknown. Herein, we report that TUSC2 protein expression is reduced/lost in GBM compared to normal brain due to protein destabilization; TUSC2 mRNA is equally expressed in both tissues. NEDD4 E3 ubiquitin ligase polyubiquitinates TUSC2 at residue K71, and the TUSC2-K71R mutant is resistant to NEDD4-mediated proteasomal degradation. Analysis of GBM specimens showed NEDD4 protein is highly expressed in GBM and the level is inversely correlated with TUSC2 protein levels. Furthermore, TUSC2 restoration induces apoptosis and inhibits patient-derived glioma stem cells (PD-GSCs) in vitro and in vivo. Conversely, TUSC2-knockout promotes PD-GSCs in vitro and in vivo. RNA-Seq analysis and subsequent validations showed GBM cells with TUSC2-knockout expressed increased Bcl-xL and were more resistant to apoptosis induced by a Bcl-xL-specific BH3 mimetic. A TUSC2-knockout gene signature created from the RNA-seq data predicts poor patient survival. Together, these findings establish that NEDD4-mediated polyubiquitination is a novel mechanism for TUSC2 degradation in GBM and that TUSC2 loss promotes GBM progression in part through Bcl-xL upregulation.
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Registered trials
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