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PMID: 16766796 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

The interaction of thioredoxin with Txnip. Evidence for formation of a mixed disulfide by disulfide exchange.

The Journal of biological chemistry ·Vol. 281 ·No. 31 ·2006-08-04 ·Pages 21884-21891

Patwari P, Higgins LJ, Chutkow WA, Yoshioka J, Lee RT

Abstract

The thioredoxin system plays an important role in maintaining a reducing environment in the cell. Recently, several thioredoxin binding partners have been identified and proposed to mediate aspects of redox signaling, but the significance of these interactions is unclear in part due to incomplete understanding of the mechanism for thioredoxin binding. Thioredoxin-interacting protein (Txnip) is critical for regulation of glucose metabolism, the only currently known function of which is to bind and inhibit thioredoxin. We explored the mechanism of the Txnip-thioredoxin interaction and present evidence that Txnip and thioredoxin form a stable disulfide-linked complex. We identified two Txnip cysteines that are important for thioredoxin binding and showed that this interaction is consistent with a disulfide exchange reaction between oxidized Txnip and reduced thioredoxin. These cysteines are not conserved in the broader family of arrestin domain-containing proteins, and we demonstrate that the thioredoxin-binding property of Txnip is unique. These data suggest that Txnip is a target of reduced thioredoxin and provide insight into the potential role of Txnip as a redox-sensitive signaling protein.

MeSH Terms
3T3-L1 Cells Animals Carrier Proteins/metabolism Cell Line Conserved Sequence Cysteine/metabolism Disulfides/metabolism Humans Mice Oxidation-Reduction Protein Binding Thioredoxins/metabolism Transfection
Chemicals
Carrier Proteins Disulfides TXNIP protein, human Thioredoxins Cysteine
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Patwari Parth
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Cambridge, Massachusetts 02139. Electronic address: ppatwari@rics.bwh.harvard.edu.
Higgins Luke J
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Cambridge, Massachusetts 02139.
Chutkow William A
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Cambridge, Massachusetts 02139.
Yoshioka Jun
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Cambridge, Massachusetts 02139.
Lee Richard T
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Cambridge, Massachusetts 02139.
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Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
0021-9258
DOI
10.1074/jbc.M600427200
Email
ppatwari@rics.bwh.harvard.edu
Published
2006-08-04
Epub
2006-00-09
Pages
21884-21891
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC1609191
Subset
IM
Grants
NHLBI NIH HHS · R01 HL073809 · United States
NHLBI NIH HHS · T32 HL007604 · United States
External Links
PubMed source DOI: 10.1074/jbc.M600427200 PMC Full Text View journal details
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