HDAC6 is a specific deacetylase of peroxiredoxins and is involved in redox regulation.
Eighteen histone deacetylases (HDACs) 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, a ubiquitin-binding site, and it selectively deacetylases alpha-tubulin and Hsp90. Here, we report the 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 H(2)O(2) 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 superoxidation, and its resistance to transition to high-molecular-mass complexes. Thus, HDAC6 and Prx are targets for modulating intracellular redox status in therapeutic strategies for disorders as disparate as cancers and neurodegenerative diseases.
Parmigiani
R B
RB
Cell Biology and Molecular Biology Programs, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
Xu
W S
WS
Venta-Perez
G
G
Erdjument-Bromage
H
H
Yaneva
M
M
Tempst
P
P
Marks
P A
PA
D000107:Acetylation; D045744:Cell Line, Tumor; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010545:Peroxides / Q000378:metabolism; D054464:Peroxiredoxins / Q000378:metabolism*
D010545:Peroxides; C515940:PRDX1 protein, human; C086065:PRDX2 protein, human; D054464:Peroxiredoxins; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases