Controversies Surrounding the Potential Use of Histone Deacetylase Inhibitors for the Treatment of Asthma

Figure 3

Metal-dependent histone deacetylase (HDAC) family. The classical HDACs are grouped into three classes based on their homology and sequence identity to yeast. Class I HDACs comprise of HDAC1, 2, 3, and 8 and these are primarily localized in the cell nucleus. Class II HDACs are divided into two subclasses. They consist of HDAC4, 5, 7, and 9 which make up Class IIa; these contain a myocyte enhancer factor-2 (MEF2)-binding motif, as shown. HDAC6 and 10 make up Class IIb and are primarily localized in the cell cytoplasm. HDAC11 shares homology with both the Class I and Class II HDACs and is the sole member of Class IV. The classical HDACs share a highly conserved deacetylase (DAC) domain shown as a long cylinder and nuclear localization signals are shown as short black cylinders. The 14-3-3 chaperone-binding motifs are shown as short grey cylinders labelled with “S” for serine phosphorylation sites. Black lines represent N- and C-terminal tails and the number of the amino acid of the longest isoform is shown. Other features shown are SE14, Ser-Glu-containing tetradecapeptide repeats; ZnF, ubiquitin-binding zinc finger; Leucine-rich domain. *HDAC2 expression is decreased in bronchial biopsies from patients with asthma; HDAC8 associates with α-actin and is essential for smooth muscle differentiation and contraction which may have implications in asthma; HDAC6 deacetylates α-tubulin and microtubules and this may have important implications in cellular activation and motility in asthma.