A short guide to histone deacetylases including recent progress on class II enzymes

Park, Suk-Youl; Kim, Ji Soo

doi:10.1038/s12276-020-0382-4

Cited by 297 publications

(233 citation statements)

References 65 publications

(84 reference statements)

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“…A study by Feng and colleagues (48) demonstrated that application of histone deacetylase (HDAC) inhibitors was able to limit RSV replication in inoculated BEAS-2B cultures. The HDAC family of proteins are pleiotropic regulators of cellular function, which includes transcriptional repression, epigenetic modification, and signal transduction (133,150). Importantly, HDACs regulate microtubule disassembly and IFT processes in cilia and are critical in control of cilia length (58,149,213).…”

Section: Respiratory Syncytial Virusmentioning

confidence: 99%

First contact: the role of respiratory cilia in host-pathogen interactions in the airways

Kuek

Lee

2020

American Journal of Physiology-Lung Cellular and Molecular Phys

127

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Respiratory cilia are the driving force of the mucociliary escalator, working in conjunction with secreted airway mucus to clear inhaled debris and pathogens from the conducting airways. Respiratory cilia are also one of the first contact points between host and inhaled pathogens. Impaired ciliary function is a common pathological feature in patients with chronic airway diseases, increasing susceptibility to respiratory infections. Common respiratory pathogens including viruses, bacteria and fungi have been shown to target cilia and/or ciliated airway epithelial cells, resulting in a disruption of mucociliary clearance that may facilitate host infection. Despite being an integral component of airway innate immunity, the role of respiratory cilia and their clinical significance during airway infections is still poorly understood. This review examines the expression, structure, and function of respiratory cilia during pathogenic infection of the airways. This review also discusses specific known points of interaction of bacteria, fungi, and viruses with respiratory cilia function. The emerging biological functions of motile cilia relating to intracellular signaling and their potential immuno-regulatory roles during infection will also be discussed.

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Section: Respiratory Syncytial Virusmentioning

confidence: 99%

First contact: the role of respiratory cilia in host-pathogen interactions in the airways

Kuek

Lee

2020

American Journal of Physiology-Lung Cellular and Molecular Phys

127

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“…Class IV is represented by HDAC11 (Haberland et al, 2009). HDACs class I, II and IV require Zinc-dependent catalysis as cofactors for their enzymatic activity and HDACs class III or Sirtuins required nicotinamide adenine dinucleotide (NAD)-dependent (Park and Kim, 2020).…”

Section: Histone Deacetylases: An Overviewmentioning

confidence: 99%

Synergistic Enhancement of Cancer Therapy Using HDAC Inhibitors: Opportunity for Clinical Trials

et al. 2020

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Chemotherapy is one of the most established and effective treatments for almost all types of cancer. However, the elevated toxicity due to the non-tumor-associated effects, development of secondary malignancies, infertility, radiation-induced fibrosis and resistance to treatment limit the effectiveness and safety of treatment. In addition, these multiple factors significantly impact quality of life. Over the last decades, our increased understanding of cancer epigenetics has led to new therapeutic approaches and the promise of improved patient outcomes. Epigenetic alterations are commonly found in cancer, especially the increased expression and activity of histone deacetylases (HDACs). Dysregulation of HDACs are critical to the development and progression of the majority of tumors. Hence, HDACs inhibitors (HDACis) were developed and now represent a very promising treatment strategy. The use of HDACis as monotherapy has shown very positive pre-clinical results, but clinical trials have had only limited success. However, combinatorial regimens with other cancer drugs have shown synergistic effects both in pre-clinical and clinical studies. At the same time, these combinations have enhanced the efficacy, reduced the toxicity and tumor resistance to therapy. In this review, we will examine examples of HDACis used in combination with other cancer drugs and highlight the synergistic effects observed in recent preclinical and clinical studies.

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“…The acetylation of p53 can be reversed by various histone deacetylases (HDACs). In humans, there are four classes of HDAC (Class I, Class IIa/b, Class III and Class IV) 76 . These classes can be divided into two families based on the conserved deacetylase domain and their specific cofactors: the HDAC family (Class I and Class IIa/b) and the sirtuin protein family (Class III and Class IV) 76 .…”

Section: -3-3 Regulation Of P53 Acetylationmentioning

confidence: 99%

“…In humans, there are four classes of HDAC (Class I, Class IIa/b, Class III and Class IV) 76 . These classes can be divided into two families based on the conserved deacetylase domain and their specific cofactors: the HDAC family (Class I and Class IIa/b) and the sirtuin protein family (Class III and Class IV) 76 . HDAC 1 (Class I) is one of the most prominent deacetylase enzymes for p53 and it represses p53-dependent transcriptional activation, cell cycle arrest and apoptosis 77 .…”

Section: -3-3 Regulation Of P53 Acetylationmentioning

confidence: 99%

Regulation of p53 by the 14-3-3 protein interaction network: new opportunities for drug discovery in cancer

et al. 2020

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Most cancers evolve to disable the p53 pathway, a key tumour suppressor mechanism that prevents transformation and malignant cell growth. However, only ~50% exhibit inactivating mutations of p53, while in the rest its activity is suppressed by changes in the proteins that modulate the pathway. Therefore, restoring p53 activity in cells in which it is still wild type is a highly attractive therapeutic strategy that could be effective in many different cancer types. To this end, drugs can be used to stabilise p53 levels by modulating its regulatory pathways. However, despite the emergence of promising strategies, drug development has stalled in clinical trials. The need for alternative approaches has shifted the spotlight to the 14-3-3 family of proteins, which strongly influence p53 stability and transcriptional activity through direct and indirect interactions. Here, we present the first detailed review of how 14-3-3 proteins regulate p53, with special emphasis on the mechanisms involved in their binding to different members of the pathway. This information will be important to design new compounds that can reactivate p53 in cancer cells by influencing protein–protein interactions. The intricate relationship between the 14-3-3 isoforms and the p53 pathway suggests that many potential drug targets for p53 reactivation could be identified and exploited to design novel antineoplastic therapies with a wide range of applications.

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A short guide to histone deacetylases including recent progress on class II enzymes

Cited by 297 publications

References 65 publications

First contact: the role of respiratory cilia in host-pathogen interactions in the airways

First contact: the role of respiratory cilia in host-pathogen interactions in the airways

Synergistic Enhancement of Cancer Therapy Using HDAC Inhibitors: Opportunity for Clinical Trials

Regulation of p53 by the 14-3-3 protein interaction network: new opportunities for drug discovery in cancer

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