Regulation of Histone Deacetylase 6 Activity via S-Nitrosylation.
Nitric oxide (NO) is a gaseous regulatory factor produced by NO synthases (NOS) and it plays several critical roles via S-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 S-nitrosylation of HDAC2 is involved in the regulation of deacetylase activity. However, it remains unknown whether other subtypes of the HDAC family are S-nitrosylated. In the present study, we found that HDAC6 is a target of NO. A biotin-switch assay revealed that endogenous HDAC6 is S-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 in vitro and increased acetylated α-tubulin, a major substrate for HDAC6, in A549 cells. These findings suggest that S-nitrosylation of HDAC6 plays a pivotal role in the regulation of protein acetylation.
Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University.
Kosaku
K
Okuda
Akihiro
A
Ito
Takashi
T
Uehara
D000107:Acetylation; D045744:Cell Line, Tumor; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D026403:S-Nitrosothiols / Q000494:pharmacology
D020030:Nitric Oxide Donors; D026403:S-Nitrosothiols; D009569:Nitric Oxide; C021315:S-nitrosocysteine; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases; D003545:Cysteine