Histone Lysine-Specific Methyltransferases and Demethylases in Carcinogenesis: New Targets for Cancer Therapy and Prevention

ISSN: 1873-4316 (Online)
ISSN: 1389-2010 (Print)


Volume 15, 12 Issues, 2014


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Current Pharmaceutical Biotechnology

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Editor-in-Chief:
Zeno Foldes-Papp
Visiting Professor of Medical Biochemistry
HELIOS Clinical Center of Emergency Medicine
Department for Internal Medicine
Alte-Koelner-Strasse 9
D-51688 Koeln-Wipperfuerth
Germany


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Histone Lysine-Specific Methyltransferases and Demethylases in Carcinogenesis: New Targets for Cancer Therapy and Prevention

Author(s): Xuejiao Tian, Saiyang Zhang, Hong-Min Liu, Yan-Bing Zhang, Christopher A Blair, Dan Mercola, Paolo Sassone-Corsi and Xiaolin Zi

Affiliation: 1Departments of Urology, 2Pharmaceutical Sciences, 3Pharmacology, 5Pathology and Laboratory medicine and 6Biological Chemistry, and, University of California, Irvine, Orange, CA 92868, USA

Abstract

Aberrant histone lysine methylation that is controlled by histone lysine methyltransferases (KMTs) and demethylases (KDMs) plays significant roles in carcinogenesis. Infections by tumor viruses or parasites and exposures to chemical carcinogens can modify the process of histone lysine methylation. Many KMTs and KDMs contribute to malignant transformation by regulating the expression of human telomerase reverse transcriptase (hTERT), forming a fused gene, interacting with proto-oncogenes or being up-regulated in cancer cells. In addition, histone lysine methylation participates in tumor suppressor gene inactivation during the early stages of carcinogenesis by regulating DNA methylation and/or by other DNA methylation independent mechanisms. Furthermore, recent genetic discoveries of many mutations in KMTs and KDMs in various types of cancers highlight their numerous roles in carcinogenesis and provide rare opportunities for selective and tumor-specific targeting of these enzymes. The study on global histone lysine methylation levels may also offer specific biomarkers for cancer detection, diagnosis and prognosis, as well as for genotoxic and non-genotoxic carcinogenic exposures and risk assessment. This review summarizes the role of histone lysine methylation in the process of cellular transformation and carcinogenesis, genetic alterations of KMTs and KDMs in different cancers and recent progress in discovery of small molecule inhibitors of these enzymes.


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Article Details

Volume: 14
First Page: 1
Last Page: 1
Page Count: 1
DOI: 10.2174/13892010113149990004
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