Histone Deacetylases: Transcriptional Regulation and Other Cellular Functions


Editor Eric Verdin , Humana Press , 2006 . ISBN: 1-588-29-499-4

In 1964, Allfrey and colleagues caused some controversy with their discovery that histone proteins could be acetylated reversibly and their proposal that they could thus regulate RNA synthesis. The first histone deacetylase (HDAC) was isolated in 1996 by Taunton and colleagues, helping to establish the role of histone acetylation in transcriptional regulation. Since 1996 there has been a rapid expansion in the investigation of these DNA regulatory proteins.

This text, in the series ‘Cancer Drug Discovery and Development’, is a timely and excellent review of the work on HDACs over the past 8 years. The genetics, structure and function of the 18 known HDACs are summarised succinctly in 11 chapters covering the three classes of these proteins. These cover not only the proteins themselves, but also their substrates and partners.

There is increasing evidence that HDACs have biological activities outside direct regulation of gene transcription. These first 11 chapters are excellent detailed summaries of this work, they are as up to date as can be expected for a textbook and are very well illustrated.

The whole of this text will be of most interest and use to postgraduate research students and research scientists. Of greatest interest to haematologists is the role of the class 1 HDACs in the regulation of the cell cycle, proliferation and differentiation. The first four and last three chapters review the increasing evidence that this class is involved in tumour formation and/or progression and that their inhibitors (HDACIs) may be beneficial in cancer therapy. In a remarkably short space of time some HDACIs are already in phase II clinical trials including some in leukaemia and lymphoma.

Class II HDACs appear to control differentiation and growth of striated muscle which is of less interest to haematologists. Except to say that one of the more difficult side-effects of one HDACI is to evoke QT and ST interval abnormalities that may limit its utility in clinical practice.

As the editor, Eric Verdin, says in his preface this book does provide a landmark summary of the work done to date on these regulatory proteins, it will help stimulate a far reaching research agenda and there is still much work to be done in the understanding of how they work and how they can be exploited in cancer therapy. This text is highly recommended to all scientists and clinicians with an interest in the future control of the cell cycle in malignant disease.