Fig. 1

Structure of the HDAC6 gene and protein. The gene-encoding HDAC6 is located in Xp11.23 (left). The HDAC6 protein (right) contains two functional catalytic domains (DD1 and DD2), which catalyze deacetylation activity for α-tubulin, HSP90, and cortactin. The nuclear export signal (NES) promotes cytoplasmic localization of the protein, and the Ser-Glu-containing tetrapeptide (SE14) region ensures stable anchorage of the enzyme in the cytoplasm. Although the HDAC6 protein contains a nuclear localization sequence (NLS), HDAC6 mainly exists in the cytoplasm owing to the actions of the NES and SE14 motifs. The ubiquitin-binding zinc finger domain (ZnF-UBP domain, also known as the PAZ, BUZ, or DAUP domain) in its C-terminal region interacts with ubiquitinated proteins and mediates the regulation of ubiquitination-mediated degradation