Thioredoxin-interacting protein (Txnip) is a feedback regulator of S-nitrosylation.

Published

Journal Article

Nitric oxide exerts a plethora of biological effects via protein S-nitrosylation, a redox-based reaction that converts a protein Cys thiol to a S-nitrosothiol. However, although the regulation of protein S-nitrosylation has been the subject of extensive study, much less is known about the systems governing protein denitrosylation. Most recently, thioredoxin/thioredoxin reductases were shown to mediate both basal and stimulus-coupled protein denitrosylation. We now demonstrate that protein denitrosylation by thioredoxin is regulated dynamically by thioredoxin-interacting protein (Txnip), a thioredoxin inhibitor. Endogenously synthesized nitric oxide represses Txnip, thereby facilitating thioredoxin-mediated denitrosylation. Autoregulation of denitrosylation thus allows cells to survive nitrosative stress. Our findings reveal that denitrosylation of proteins is dynamically regulated, establish a physiological role for thioredoxin in protection from nitrosative stress, and suggest new approaches to manipulate cellular S-nitrosylation.

Full Text

Duke Authors

Cited Authors

  • Forrester, MT; Seth, D; Hausladen, A; Eyler, CE; Foster, MW; Matsumoto, A; Benhar, M; Marshall, HE; Stamler, JS

Published Date

  • December 25, 2009

Published In

Volume / Issue

  • 284 / 52

Start / End Page

  • 36160 - 36166

PubMed ID

  • 19847012

Pubmed Central ID

  • 19847012

Electronic International Standard Serial Number (EISSN)

  • 1083-351X

Digital Object Identifier (DOI)

  • 10.1074/jbc.M109.057729

Language

  • eng

Conference Location

  • United States