The KDM5 family of histone demethylases as targets in oncology drug discovery
| Autor: | Peter Birk Rasmussen, Peter Staller |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Jumonji Domain-Containing Histone Demethylases
Cancer Research Histone deacetylase 2 Nuclear Proteins Antineoplastic Agents Biology Cell biology Gene Expression Regulation Neoplastic Histones Repressor Proteins Histone H3 Biochemistry Drug Design Neoplasms Histone methyltransferase Histone methylation Histone H2A Genetics Animals Humans Histone Demethylases Cancer epigenetics Enzyme Inhibitors Retinoblastoma-Binding Protein 2 Histone demethylase activity |
| Zdroj: | Epigenomics. 6:277-286 |
| ISSN: | 1750-192X 1750-1911 |
| DOI: | 10.2217/epi.14.14 |
| Popis: | There is growing evidence for a causal role of the KDM5 family of histone demethylases in human cancer. In particular, KDM5A (JARID1A/RBP2) and KDM5B (JARID1B/PLU1) contribute to cancer cell proliferation, reduce the expression of tumor suppressor genes, promote the development of drug tolerance and maintain tumor-initiating cells. KDM5 enzymes remove tri- and di-methylations of lysine 4 of histone H3 – modifications that occur at the start site of transcription in actively transcribed genes. However, the importance of the histone demethylase activity of KDM5 proteins for cancer cells has not been resolved so far. The currently available approaches suppress or remove the targeted proteins and thereby affect their putative functions as structural components and recruitment factors for other chromatin-associated proteins. Therefore, the development of specific enzymatic inhibitors for KDM5 will promote our understanding of the biological role of their catalytic activity and yield potential novel anticancer therapeutics. |
| Databáze: | OpenAIRE |
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