Regulation of Histone Deacetylase 6 Activity <i>via</i> <i>S</i>-Nitrosylation
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Nitric oxide (NO) is a gaseous regulatory factor produced by NO synthases (NOS) and it plays several critical roles <i>via</i> <i>S</i>-nitrosylation of protein cysteine residues. Histone deacetylase (HDAC) functions in the maintenance/balance of chromatin acetylation and contributes to transcriptional supression. It has been reported that <i>S</i>-nitrosylation of HDAC2 is involved in the regulation of deacetylase activity. However, it remains unknown whether other subtypes of the HDAC family are <i>S</i>-nitrosylated. In the present study, we found that HDAC6 is a target of NO. A biotin-switch assay revealed that endogenous HDAC6 is <i>S</i>-nitrosylated by both NO donors and NO derived from the inducible type of NOS in cells treated with cytokines. NO led to suppressed deacetylase activity <i>in vitro</i> and increased acetylated α-tubulin, a major substrate for HDAC6, in A549 cells. These findings suggest that <i>S</i>-nitrosylation of HDAC6 plays a pivotal role in the regulation of protein acetylation.
- Biological and Pharmaceutical Bulletin
Biological and Pharmaceutical Bulletin 38(9), 1434-1437, 2015
The Pharmaceutical Society of Japan