title: Identification of Redox and Glucose-Dependent Txnip Protein Interactions.
abstract: 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.
authors.affiliation: Children's Health Research Center, Sanford Research, Sioux Falls, SD 57104, USA.
authors.forename: Benjamin J
authors.identifier: 0000-0002-5340-6886
authors.initials: BJ
authors.lastname: Forred
authors.affiliation: Children's Health Research Center, Sanford Research, Sioux Falls, SD 57104, USA.
authors.forename: Skyla
authors.initials: S
authors.lastname: Neuharth
authors.affiliation: Children's Health Research Center, Sanford Research, Sioux Falls, SD 57104, USA.
authors.forename: Dae In
authors.initials: DI
authors.lastname: Kim
authors.affiliation: Children's Health Research Center, Sanford Research, Sioux Falls, SD 57104, USA.
authors.forename: Michael W
authors.identifier: 0000-0002-4133-7510
authors.initials: MW
authors.lastname: Amolins
authors.affiliation: Proteomics Facility, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
authors.forename: Khatereh
authors.initials: K
authors.lastname: Motamedchaboki
authors.affiliation: Children's Health Research Center, Sanford Research, Sioux Falls, SD 57104, USA; Department of Pediatrics, Sanford School of Medicine, The University of South Dakota, Sioux Falls, SD 57105, USA.
authors.forename: Kyle J
authors.initials: KJ
authors.lastname: Roux
authors.affiliation: Children's Health Research Center, Sanford Research, Sioux Falls, SD 57104, USA; Department of Pediatrics, Sanford School of Medicine, The University of South Dakota, Sioux Falls, SD 57105, USA.
authors.forename: Peter F
authors.identifier: 0000-0001-5344-9192
authors.initials: PF
authors.lastname: Vitiello
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D010084:Oxidation-Reduction / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D025941:Protein Interaction Mapping
chemical_list: D002352:Carrier Proteins; C486715:TXNIP protein, human; D005947:Glucose