Abstract 1742: Potential roles of histone deacetylase 11 in cell cycle regulation and cancer
| Autor: | Elphine Telles, Thejal Srikumar, Edward Seto |
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| Rok vydání: | 2013 |
| Předmět: | |
| Zdroj: | Cancer Research. 73:1742-1742 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.am2013-1742 |
| Popis: | Histone deacetylases (HDACs) are enzymes that deacetylate lysine residues on histone and non-histone proteins. They regulate various cellular functions including transcriptional regulation, cell proliferation, apoptosis, and cellular metabolism. Broad spectrum HDAC inhibitors, including Vorinostat and Romidepsin, have been approved for cancer therapy, but their use is limited due to toxicity and side effects. A deeper understanding of the function of individual histone deacetylases could lead to the development of more specific and potentially more effective anti-cancer agents. In this context, Histone Deacetylase 11 (HDAC11) could be a potential target for anticancer therapeutics. HDAC11 is the most recently discovered Histone Deacetylase and, therefore, the least characterized among the 18 HDACs. Its expression is altered in various cancers and recent studies have suggested that HDAC11 might inhibit the activity and function of the DNA replication licensing factor Cdt1. To examine whether HDAC11 controls Cdt1-mediated cell cycle regulation, HDAC11 was overexpressed in human U87 glioblastoma cells. We found that overexpression of HDAC11 represses Cdt1 expression levels. Most importantly, we observed that HDAC11 overexpression promotes earlier cell entry into the G2/M phase of the cell cycle than non-HDAC11-overexpressed cells. Finally, we discovered that HDAC11 levels change throughout the cell cycle in a manner that is contrary to the Cdt1 expression levels. These results indicate that HDAC11 negatively regulates Cdt1, and uncover an important and previously unknown role of this enzyme in cell cycle regulation. Together, our findings suggest that development of drugs that target HDAC11 might be a viable strategy for overcoming cancers where this protein is overexpressed. Citation Format: Thejal Srikumar, Elphine Telles, Edward Seto. Potential roles of histone deacetylase 11 in cell cycle regulation and cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1742. doi:10.1158/1538-7445.AM2013-1742 |
| Databáze: | OpenAIRE |
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