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Antioxid Redox Signal. 2012 Mar 15;16(6):587-96. doi: 10.1089/ars.2011.4137. Epub 2011 Dec 20.

Thioredoxin interacting protein: redox dependent and independent regulatory mechanisms.

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  • 1Department of Medicine, Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, New York 14642, USA.



The thioredoxin-interacting protein (TXNIP, also termed VDUP1 for vitamin D upregulated protein or TBP2 for thioredoxin-binding protein) was originally discovered by virtue of its strong regulation by vitamin D. Recently, TXNIP has been found to regulate the cellular reduction-oxidation (redox) state by binding to and inhibiting thioredoxin (TRX) in a redox-dependent fashion.


Studies of the Hcb-19 mouse, TXNIP nonsense mutated mouse, demonstrate redox-mediated roles in lipid and glucose metabolism, cardiac function, inflammation, and carcinogenesis. Exciting recent data indicate important roles for TXNIP in redox independent signaling. Specifically, sequence analysis revealed that TXNIP is a member of the classical visual/β-arrestin superfamily, and is one of the six members of the arrestin domain-containing (ARRDC, or α-arrestin) family.


Although the function of α-arrestins is not well known, recent studies suggest roles in endocytosis and protein ubiquitination through PPxY motifs in their C-terminal tails. Importantly, the ability of TXNIP to inhibit glucose uptake was found to be independent of TRX binding. Further investigation showed that several metabolic functions of TXNIP were due to the arrestin domains, thus further supporting the importance of redox independent functions of TXNIP.


Since TXNIP transcription and protein stability are highly regulated by multiple tissue-specific stimuli, it appears that TXNIP should be a good therapeutic target for metabolic diseases.

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