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Oxidative Medicine and Cellular Longevity
Volume 2016, Article ID 5829063, 10 pages
Research Article

Identification of Redox and Glucose-Dependent Txnip Protein Interactions

1Children’s Health Research Center, Sanford Research, Sioux Falls, SD 57104, USA
2Proteomics Facility, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA
3Department of Pediatrics, Sanford School of Medicine, The University of South Dakota, Sioux Falls, SD 57105, USA

Received 25 March 2016; Accepted 26 May 2016

Academic Editor: Mikko O. Laukkanen

Copyright © 2016 Benjamin J. Forred et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Thioredoxin-interacting protein (Txnip) acts as a negative regulator of thioredoxin function and is a critical modulator of several diseases including, but not limited to, diabetes, ischemia-reperfusion cardiac injury, and carcinogenesis. Therefore, Txnip has become an attractive therapeutic target to alleviate disease pathologies. Although Txnip has been implicated with numerous cellular processes such as proliferation, fatty acid and glucose metabolism, inflammation, and apoptosis, the molecular mechanisms underlying these processes are largely unknown. The objective of these studies was to identify Txnip interacting proteins using the proximity-based labeling method, BioID, to understand differential regulation of pleiotropic Txnip cellular functions. The BioID transgene fused to Txnip expressed in HEK293 identified 31 interacting proteins. Many protein interactions were redox-dependent and were disrupted through mutation of a previously described reactive cysteine (C247S). Furthermore, we demonstrate that this model can be used to identify dynamic Txnip interactions due to known physiological regulators such as hyperglycemia. These data identify novel Txnip protein interactions and demonstrate dynamic interactions dependent on redox and glucose perturbations, providing clarification to the pleiotropic cellular functions of Txnip.