The ECS(SPSB) E3 ubiquitin ligase is the master regulator of the lifetime of inducible nitric-oxide synthase

Kazuma Matsumoto, Tadashi Nishiya, Satoshi Maekawa, Takahiro Horinouchi, Kouetsu Ogasawara, Takashi Uehara, Soichi Miwa

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The ubiquitin-proteasome pathway is an important regulatory system for the lifetime of inducible nitric-oxide synthase (iNOS), a high-output isoform compared to neuronal NOS (nNOS) and endothelial NOS (eNOS), to prevent overproduction of NO that could trigger detrimental effects such as cytotoxicity. Two E3 ubiquitin ligases, Elongin B/C-Cullin-5-SPRY domain- and SOCS box-containing protein [ECS(SPSB)] and the C-terminus of Hsp70-interacting protein (CHIP), recently have been reported to target iNOS for proteasomal degradation. However, the significance of each E3 ubiquitin ligase for the proteasomal degradation of iNOS remains to be determined. Here, we show that ECS(SPSB) specifically interacted with iNOS, but not nNOS and eNOS, and induced the subcellular redistribution of iNOS from dense regions to diffused expression as well as the ubiquitination and proteasomal degradation of iNOS, whereas CHIP neither interacted with iNOS nor had any effects on the subcellular localization, ubiquitination, and proteasomal degradation of iNOS. These results differ from previous reports. Furthermore, the lifetime of the iNOS(N27A) mutant, a form of iNOS that does not bind to ECS(SPSB), was substantially extended in macrophages. These results demonstrate that ECS(SPSB), but not CHIP, is the master regulator of the iNOS lifetime.

Original languageEnglish
Pages (from-to)46-51
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume409
Issue number1
DOIs
Publication statusPublished - May 27 2011

Fingerprint

Ubiquitin-Protein Ligases
Nitric Oxide Synthase Type II
Degradation
Ubiquitination
Proteins
Cullin Proteins
Macrophages
Proteasome Endopeptidase Complex
Cytotoxicity
Ubiquitin
Protein Isoforms

Keywords

  • CHIP
  • ECS(SPSB)
  • INOS
  • Proteasomal degradation
  • Ubiquitination

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

The ECS(SPSB) E3 ubiquitin ligase is the master regulator of the lifetime of inducible nitric-oxide synthase. / Matsumoto, Kazuma; Nishiya, Tadashi; Maekawa, Satoshi; Horinouchi, Takahiro; Ogasawara, Kouetsu; Uehara, Takashi; Miwa, Soichi.

In: Biochemical and Biophysical Research Communications, Vol. 409, No. 1, 27.05.2011, p. 46-51.

Research output: Contribution to journalArticle

Matsumoto, Kazuma ; Nishiya, Tadashi ; Maekawa, Satoshi ; Horinouchi, Takahiro ; Ogasawara, Kouetsu ; Uehara, Takashi ; Miwa, Soichi. / The ECS(SPSB) E3 ubiquitin ligase is the master regulator of the lifetime of inducible nitric-oxide synthase. In: Biochemical and Biophysical Research Communications. 2011 ; Vol. 409, No. 1. pp. 46-51.
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