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.
Schemies
Jörg
J
Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany.
Sippl
Wolfgang
W
Jung
Manfred
M
D000107:Acetylation; D001665:Binding Sites; D044127:Epigenesis, Genetic; D000073864:Histone Deacetylase 6; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry / Q000494:pharmacology; D007555:Isoxazoles / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D009281:Naphthalenes / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D011753:Pyrones / Q000737:chemistry / Q000494:pharmacology; D056565:Sirtuin 2; D037761:Sirtuins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism*; D050257:Tubulin Modulators / Q000737:chemistry / Q000494:pharmacology*
D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007555:Isoxazoles; D009281:Naphthalenes; D011753:Pyrones; D014230:Triazoles; D014404:Tubulin; D050257:Tubulin Modulators; C444426:splitomicin; C474199:SIRT2 protein, human; D056565:Sirtuin 2; D037761:Sirtuins; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases