Regulation of histone deacetylase 6 activity via S-nitrosylation

Kosaku Okuda, Akihiro Ito, Takashi Uehara

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1434-1437
Number of pages4
JournalBiological and Pharmaceutical Bulletin
Volume38
Issue number9
Publication statusPublished - Sep 1 2015

Fingerprint

Histone Deacetylases
Nitric Oxide
Acetylation
Nitric Oxide Synthase
Nitric Oxide Donors
Protein S
Tubulin
Biotin
Chromatin
Cysteine
Maintenance
Cytokines
Proteins

Keywords

  • Acetylated α-tubulin
  • Histone deacetylase 6
  • Nitric oxide
  • S-nitrosylation

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Pharmacology

Cite this

Regulation of histone deacetylase 6 activity via S-nitrosylation. / Okuda, Kosaku; Ito, Akihiro; Uehara, Takashi.

In: Biological and Pharmaceutical Bulletin, Vol. 38, No. 9, 01.09.2015, p. 1434-1437.

Research output: Contribution to journalArticle

@article{3a1a0ee4f7b946ac8ae3bce92186b6ab,
title = "Regulation of histone deacetylase 6 activity via S-nitrosylation",
abstract = "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.",
keywords = "Acetylated α-tubulin, Histone deacetylase 6, Nitric oxide, S-nitrosylation",
author = "Kosaku Okuda and Akihiro Ito and Takashi Uehara",
year = "2015",
month = "9",
day = "1",
language = "English",
volume = "38",
pages = "1434--1437",
journal = "Biological and Pharmaceutical Bulletin",
issn = "0918-6158",
publisher = "Pharmaceutical Society of Japan",
number = "9",

}

TY - JOUR

T1 - Regulation of histone deacetylase 6 activity via S-nitrosylation

AU - Okuda, Kosaku

AU - Ito, Akihiro

AU - Uehara, Takashi

PY - 2015/9/1

Y1 - 2015/9/1

N2 - 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.

AB - 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.

KW - Acetylated α-tubulin

KW - Histone deacetylase 6

KW - Nitric oxide

KW - S-nitrosylation

UR - http://www.scopus.com/inward/record.url?scp=84941032637&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84941032637&partnerID=8YFLogxK

M3 - Article

C2 - 26328501

AN - SCOPUS:84941032637

VL - 38

SP - 1434

EP - 1437

JO - Biological and Pharmaceutical Bulletin

JF - Biological and Pharmaceutical Bulletin

SN - 0918-6158

IS - 9

ER -