Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 69, Issue 13, Pages 2173-2187Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-012-0921-9
Keywords
HDAC; Cell cycle; Differentiation; Development; Chromatin; HDAC inhibitors; Deacetylation; Transcription factors
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Funding
- Novartis Research Foundation
- SystemsX RTD
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Class I Histone deacetylases (HDACs) play a central role in controlling cell cycle regulation, cell differentiation, and tissue development. These enzymes exert their function by deacetylating histones and a growing number of non-histone proteins, thereby regulating gene expression and several other cellular processes. Class I HDACs comprise four members: HDAC1, 2, 3, and 8. Deletion and/or overexpression of these enzymes in mammalian systems has provided important insights about their functions and mechanisms of action which are reviewed here. In particular, unique as well as redundant functions have been identified in several paradigms. Studies with small molecule inhibitors of HDACs have demonstrated the medical relevance of these enzymes and their potential as therapeutic targets in cancer and other pathological conditions. Going forward, better understanding the specific role of individual HDACs in normal physiology as well as in pathological settings will be crucial to exploit this protein family as a useful therapeutic target in a range of diseases. Further dissection of the pathways they impinge on and of their targets, in chromatin or otherwise, will form important avenues of research for the future.
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