Histone deacetylase inhibitors that target tubulin

Epigenetics is defined as heritable changes in gene expression that occur without changes in DNA sequence. Major mechanisms of epigenetics are post-translational histone modifications such as reversible acetylation. Histone deacetylases (HDACS) maintain the acetylation level of histones but also act on non-histone substrates that are involved in signal transduction or cellular transport processes. One important non-histone substrate is tubulin. The isotypes responsible for tubulin deacetylation are HDAC6 and the NAD(+)-dependent histone deacetylase (sirtuin) Sirt2. Here we review the action of those enzymes on tubulin and present an overview over existing inhibitors with a focus on their structural interaction with the targets. (C) 2009 Elsevier Ireland Ltd. All rights reserved.