ArticleMolecular cell2014
HDAC6 deacetylates and ubiquitinates MSH2 to maintain proper levels of MutSα.
Article in Molecular cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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Who cites it
95 citing papers in PubMed, 159 citations in OpenAlex.
- Replication associated nuclear DNA mismatch repair across kingdoms.Biochemical Society transactions · 2026Review
- Quinazolinone and Phthalazinone Inhibitors of the HDAC6/Ubiquitin Protein-Protein Interaction.Chembiochem : a European journal of chemical biology · 2026Article
- Histone deacetylase 6 deacetylates and ubiquitinates ATG3 to regulate autophagy.Cell death and differentiation · 2026Article
- Inflammation Drives Phosphorylation and Acetylation of MutS Homolog 3 and Interaction with Cytosolic HDAC6.Journal of Cancer · 2026Article
- Quinazolinone and Phthalazinone Inhibitors of the HDAC6/Ubiquitin Protein-Protein Interaction.bioRxiv : the preprint server for biology · 2025Article
- 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
- Interactome Profiling of a Lysine Deacetylase Trapping Probe Library Uncovers Crosstalk Between HDAC6 and NF-κB Signaling.Angewandte Chemie (International ed. in English) · 2025Article
- Proteomics-Based Trapping to Study Substrates of Histone Deacetylase 6 Catalytic Domain 1.Biochemistry · 2025Article
- Post-translational modifications in DNA damage repair: mechanisms underlying temozolomide resistance in glioblastoma.Oncogene · 2025Review
- Rhythmic TDP-43 affects RNA splicing of USP13, resulting in alteration of BMAL1 ubiquitination.The Journal of cell biology · 2025Article
- CITK modulates BRCA1 recruitment at DNA double strand breaks sites through HDAC6.Cell death & disease · 2025Article
- Protein arginine methyltransferase 6 enhances immune checkpoint blockade efficacy via the STING pathway in MMR-proficient colorectal cancer.Journal for immunotherapy of cancer · 2025Article
- Article
- The regulatory mechanisms and treatment of HDAC6 in immune dysregulation diseases.Frontiers in immunology · 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
- The ubiquitin ligase UBR4 and the deubiquitylase USP5 modulate the stability of DNA mismatch repair protein MLH1.The Journal of biological chemistry · 2024Article
- Mechanistic Sequence of Histone Deacetylase Inhibitors and Radiation Treatment: An Overview.Pharmaceuticals (Basel, Switzerland) · 2024Review
- MRE11A: a novel negative regulator of human DNA mismatch repair.Cellular & molecular biology letters · 2024Article
- Effect of ubiquitin protease system on DNA damage response in prostate cancer (Review).Experimental and therapeutic medicine · 2024Review
35 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
32 authors at 10 institutions in 3 countries.
Funding
Abstract
MutS protein homolog 2 (MSH2) is a key DNA mismatch repair protein. It forms the MSH2-MSH6 (MutSα) and MSH2-MSH3 (MutSβ) heterodimers, which help to ensure genomic integrity. MutSα not only recognizes and repairs mismatched nucleotides but also recognizes DNA adducts induced by DNA-damaging agents, and triggers cell-cycle arrest and apoptosis. Loss or depletion of MutSα from cells leads to microsatellite instability (MSI) and resistance to DNA damage. Although the level of MutSα can be reduced by the ubiquitin-proteasome pathway, the detailed mechanisms of this regulation remain elusive. Here we report that histone deacetylase 6 (HDAC6) sequentially deacetylates and ubiquitinates MSH2, leading to MSH2 degradation. In addition, HDAC6 significantly reduces cellular sensitivity to DNA-damaging agents and decreases cellular DNA mismatch repair activities by downregulation of MSH2. Overall, these findings reveal a mechanism by which proper levels of MutSα are maintained.
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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.