HDAC6 is a specific deacetylase of peroxiredoxins and is involved in redox regulation

A19 Eighteen histone deacetylases (HDAC) are present in humans, categorized into two groups: zinc dependent enzymes (HDAC1-11) and NAD+ dependent enzymes (Sirtuins 1-7). Among zinc dependent HDACs, HDAC6 is unique. It has a cytoplasmic localization, two catalytic sites, an ubiquitin binding site and selectively deacetylases α-tubulin and HSP90. Here we report the novel discovery that the redox regulatory proteins, peroxiredoxin (Prx) I and Prx II are specific targets of HDAC6. Prx are antioxidants enzymes whose main function is H2O2 reduction. Prx are elevated in many cancers and neurodegenerative diseases. The acetylated form of Prx accumulates in the absence of an active HDAC6. Acetylation of Prx increases its reducing activity, its resistance to super oxidation and its resistance to transition to high molecular weight complexes. Thus, HDAC6 and Prx are targets for modulating intracellular redox status in therapeutic strategies for disorders as disparate as cancers and neurodegenerative diseases.