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Thioredoxin interacting protein (Txnip) is feedback regulator of S‐nitrosylation
Author(s) -
Forrester Michael T,
Seth Divya,
Hausladen Alfred,
Eyler Christine E,
Foster Matthew W,
Matsumoto Akio,
Benhar Moran,
Marshall Harvey E,
Stamler Jonathan S
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.904.2
Subject(s) - txnip , thioredoxin , thioredoxin interacting protein , nitrosylation , s nitrosylation , microbiology and biotechnology , nitric oxide , regulator , chemistry , biology , biochemistry , oxidative stress , cysteine , gene , organic chemistry , enzyme
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, while 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.