ArticlePloS one2014
GSK3A is redundant with GSK3B in modulating drug resistance and chemotherapy-induced necroptosis.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 29 citations in OpenAlex.
- A system-wide investigation into the phosphoregulatory network of TNIK and its cellular implications.Frontiers in bioinformatics · 2026Article
- Trigger Points of Necroptosis (RIPK1, RIPK3, and MLKL)-Promising Horizon or Blind Alley in Therapy of Colorectal Cancer?International journal of molecular sciences · 2025Review
- GSK3A promotes human adenovirus replication and phosphorylates viral L4-22K protein.Life science alliance · 2025Article
- The Expression Profile of Wnt/β-Catenin Signalling Pathway Genes in Miscarriages.Balkan journal of medical genetics : BJMG · 2025Article
- TargetingJournal for immunotherapy of cancer · 2024Article
- In vitro analysis of PI3K pathway activation genes for exploring novel biomarkers and therapeutic targets in clear cell renal carcinoma.American journal of translational research · 2023Article
- Social isolation reinforces aging-related behavioral inflexibility by promoting neuronal necroptosis in basolateral amygdala.Molecular psychiatry · 2022Article
- The Impact of Oxidative Stress and AKT Pathway on Cancer Cell Functions and Its Application to Natural Products.Antioxidants (Basel, Switzerland) · 2022Review
- Non-Canonical Programmed Cell Death in Colon Cancer.Cancers · 2022Review
- From Causal Networks to Adverse Outcome Pathways: A Developmental Neurotoxicity Case Study.Frontiers in toxicology · 2022Article
- Emerging actionable targets to treat therapy-resistant colorectal cancers.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- GSK3α: An Important Paralog in Neurodegenerative Disorders and Cancer.Biomolecules · 2020Review
- Molecular and Cellular Complexity of Glioma. Focus on Tumour Microenvironment and the Use of Molecular and Imaging Biomarkers to Overcome Treatment Resistance.International journal of molecular sciences · 2020Review
- Non-invasive Potential Circulating mRNA Markers for Colorectal Adenoma Using Targeted Sequencing.Scientific reports · 2019Article
- Inferring Novel Tumor Suppressor Genes with a Protein-Protein Interaction Network and Network Diffusion Algorithms.Molecular therapy. Methods & clinical development · 2018Article
- TAAR1 induces a disturbed GSK3β phosphorylation in recurrent miscarriages through the ODC.Endocrine connections · 2018Article
- A Chemical-Genetic Approach Reveals the Distinct Roles of GSK3α and GSK3β in Regulating Embryonic Stem Cell Fate.Developmental cell · 2017Article
- Article
- GSK-3β inhibitor TWS119 attenuates rtPA-induced hemorrhagic transformation and activates the Wnt/β-catenin signaling pathway after acute ischemic stroke in rats.Molecular neurobiology · 2016Article
- MicroRNA-101 reverses temozolomide resistance by inhibition of GSK3β in glioblastoma.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glycogen Synthase Kinase-3 alpha (GSK3A) and beta (GSK3B) isoforms are encoded by distinct genes, are 98% identical within their kinase domain and perform similar functions in several settings; however, they are not completely redundant and, depending on the cell type and differentiative status, they also play unique roles. We recently identified a role for GSK3B in drug resistance by demonstrating that its inhibition enables necroptosis in response to chemotherapy in p53-null drug-resistant colon carcinoma cells. We report here that, similarly to GSK3B, also GSK3A silencing/inhibition does not affect cell proliferation or cell cycle but only abolishes growth after treatment with DNA-damaging chemotherapy. In particular, blocking GSK3A impairs DNA repair upon exposure to DNA-damaging drugs. As a consequence, p53-null cells overcome their inability to undergo apoptosis and mount a necroptotic response, characterized by absence of caspase activation and RIP1-independent, PARP-dependent AIF nuclear re-localization. We therefore conclude that GSK3A is redundant with GSK3B in regulating drug-resistance and chemotherapy-induced necroptosis and suggest that inhibition of only one isoform, or rather partial inhibition of overall cellular GSK3 activity, is enough to re-sensitize drug-resistant cells to chemotherapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.