ArticleOxidative medicine and cellular longevity2016
Histone Deacetylase Inhibitors Increase p27(Kip1) by Affecting Its Ubiquitin-Dependent Degradation through Skp2 Downregulation.
Article in Oxidative medicine and cellular longevity, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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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
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.
- Combination therapy in combating cancer.Oncotarget · 2017Pooled it
- p27Cells · 2025Article
- p57International journal of molecular sciences · 2024Article
- Histone Deacetylases in Retinoblastoma.International journal of molecular sciences · 2024Review
- SKping cell cycle regulation: role of ubiquitin ligase SKP2 in hematological malignancies.Frontiers in oncology · 2024Review
- A Beckwith-Wiedemann-AssociatedInternational journal of molecular sciences · 2021Article
- MicroRNA-186 targets SKP2 to induce p27The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2019Article
- Transducin-like enhancer of split 3 regulates proliferation of melanoma cells via histone deacetylase activity.Oncotarget · 2019Article
- Silencing heme oxygenase-1 increases the sensitivity of ABC-DLBCL cells to histone deacetylase inhibitorOncotarget · 2017Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Histone deacetylase inhibitors (HDACIs) represent an intriguing class of pharmacologically active compounds. Currently, some HDACIs are FDA approved for cancer therapy and many others are in clinical trials, showing important clinical activities at well tolerated doses. HDACIs also interfere with the aging process and are involved in the control of inflammation and oxidative stress. In vitro, HDACIs induce different cellular responses including growth arrest, differentiation, and apoptosis. Here, we evaluated the effects of HDACIs on p27(Kip1), a key cyclin-dependent kinase inhibitor (CKI). We observed that HDACI-dependent antiproliferative activity is associated with p27(Kip1) accumulation due to a reduced protein degradation. p27(Kip1) removal requires a preliminary ubiquitination step due to the Skp2-SCF E3 ligase complex. We demonstrated that HDACIs increase p27(Kip1) stability through downregulation of Skp2 protein levels. Skp2 decline is only partially due to a reduced Skp2 gene expression. Conversely, the protein decrease is more profound and enduring compared to the changes of Skp2 transcript. This argues for HDACIs effects on Skp2 protein posttranslational modifications and/or on its removal. In summary, we demonstrate that HDACIs increase p27(Kip1) by hampering its nuclear ubiquitination/degradation. The findings might be of relevance in the phenotypic effects of these compounds, including their anticancer and aging-modulating activities.
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