S-Nitrosylation of IRP2 Regulates Its Stability via the Ubiquitin-Proteasome Pathway

Sangwon Kim, Simon S. Wing, Prem Ponka

Research output: Contribution to journalArticlepeer-review

Abstract

Nitric oxide (NO) is an important signaling molecule that interacts with different targets depending on its redox state. NO can interact with thiol groups resulting in S-nitrosylation of proteins, but the functional implications of this modification are not yet fully understood. We have reported that treatment of RAW 264.7 cells with NO caused a decrease in levels of iron regulatory protein 2 (IRP2), which binds to iron-responsive elements present in untranslated regions of mRNAs for several proteins involved in iron metabolism. In this study, we show that NO causes S-nitrosylation of IRP2, both in vitro and in vivo, and this modification leads to IRP2 ubiquitination followed by its degradation in the proteasome. Moreover, mutation of one cysteine (C178S) prevents NO-mediated degradation of IRP2. Hence S-nitrosylation is a novel signal for IRP2 degradation via the ubiquitin-proteasome pathway.

Original languageEnglish (US)
Pages (from-to)330-337
Number of pages8
JournalMolecular and cellular biology
Volume24
Issue number1
DOIs
StatePublished - Jan 2004
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'S-Nitrosylation of IRP2 Regulates Its Stability via the Ubiquitin-Proteasome Pathway'. Together they form a unique fingerprint.

Cite this