ArticleCells2020
HDAC6 Regulates Radiosensitivity of Non-Small Cell Lung Cancer by Promoting Degradation of Chk1.
Article in Cells, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Geno-guided targeting of ferroptosis: a multi-layered network to overcome radioresistance in lung cancer.Frontiers in cell and developmental biology · 2026Review
- Design and synthesis of novel HDAC6 inhibitor dimer as HDAC6 degrader for cancer treatment by palladium catalysed dimerisation.Journal of enzyme inhibition and medicinal chemistry · 2025Article
- Mechanisms Underlying Radioresistance and Reversal Strategies in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2025Review
- Proteomics-Based Trapping to Study Substrates of Histone Deacetylase 6 Catalytic Domain 1.Biochemistry · 2025Article
- FOXM1 Promotes Non-Small Cell Lung Cancer Progression by Increasing CHEK1 Expression.Current medical science · 2025Article
- Histone Deacetylase 6 (HDAC6) in Ciliopathies: Emerging Insights and Therapeutic Implications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- The Role of HDAC6 in Glioblastoma Multiforme: A New Avenue to Therapeutic Interventions?Biomedicines · 2024Review
- Effects of a novel HDAC6-selective inhibitor's radiosensitization on cancer cells.Molecular biology reports · 2024Article
- Advances of E3 ligases in lung cancer.Biochemistry and biophysics reports · 2024Review
- Selective HDAC6 Inhibition Has the Potential for Anti-Cancer Effect in Renal Cell Carcinoma.Journal of personalized medicine · 2024Article
- The Mechanism of Ubiquitination or Deubiquitination Modifications in Regulating Solid Tumor Radiosensitivity.Biomedicines · 2023Review
- Preclinical Research of Stem Cells: Challenges and Progress.Stem cell reviews and reports · 2023Review
- Ricolinostat enhances adavosertib‑induced mitotic catastrophe in TP53‑mutated head and neck squamous cell carcinoma cells.International journal of oncology · 2022Article
- Epigenetic histone acetylation modulating prenatal Poly I:C induced neuroinflammation in the prefrontal cortex of rats: a study in a maternal immune activation model.Frontiers in cellular neuroscience · 2022Article
- Posttranslational modification and beyond: interplay between histone deacetylase 6 and heat-shock protein 90.Molecular medicine (Cambridge, Mass.) · 2021Review
- Implications of the USP10-HDAC6 axis in lung cancer - A path to precision medicine.Journal of cancer biology · 2021Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
We have previously discovered that HDAC6 regulates the DNA damage response (DDR) via modulating the homeostasis of a DNA mismatch repair protein, MSH2, through HDAC6's ubiquitin E3 ligase activity. Here, we have reported HDAC6's second potential E3 ligase substrate, a critical cell cycle checkpoint protein, Chk1. We have found that HDAC6 and Chk1 directly interact, and that HDAC6 ubiquitinates Chk1 in vivo and in vitro. Specifically, HDAC6 interacts with Chk1 via the DAC1 domain, which contains its ubiquitin E3 ligase activity. During the cell cycle, Chk1 protein levels fluctuate, peaking at the G2 phase, subsequently resolving via the ubiquitin-proteasome pathway, and thereby allowing cells to progress to the M phase. However, in HDAC6 knockdown non-small cell lung cancer (NSCLC) cells, Chk1 is constitutively active and fails to resolve post-ionizing radiation (IR), and this enhanced Chk1 activity leads to preferential G2 arrest in HDAC6 knockdown cells accompanied by a reduction in colony formation capacity and viability. Depletion or pharmacological inhibition of Chk1 in HDAC6 knockdown cells reverses this radiosensitive phenotype, suggesting that the radiosensitivity of HDAC6 knockdown cells is dependent on increased Chk1 kinase activity. Overall, our results highlight a novel mechanism of Chk1 regulation at the post-translational level, and a possible strategy for sensitizing NSCLC to radiation via inhibiting HDAC6's E3 ligase activity.
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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.