Physiological and Pathophysiological Roles of Thioredoxin Interacting Protein: A Perspective on Redox Inflammation and Metabolism

Overview

Journal Antioxid Redox Signal

Specialty Endocrinology

Date 2022 Jun 27

PMID 35754346

Authors

Sezin Dagdeviren

Richard T Lee

Ning Wu

Affiliations

Soon will be listed here.

Abstract

Thioredoxin interacting protein (TXNIP) is a member of the arrestin fold superfamily with important cellular functions, including cellular transport, mitochondrial energy generation, and protein cycling. It is the only arrestin-domain protein known to covalently bind to thioredoxin and plays roles in glucose metabolism, inflammation, apoptosis, and cancer. The crystal structure of the TXNIP-thioredoxin complex provided details about this fascinating interaction. Recent studies showed that TXNIP is induced by endoplasmic reticulum (ER) stress, activates NLR family pyrin domain containing 3 (NLRP3) inflammasomes, and can regulate glucose transport into cells. The tumor suppressor role of TXNIP in various cancer types and the role of TXNIP in fructose absorption are now described. The influence of TXNIP on redox state is more complex than its interaction with thioredoxin. It is incompletely understood which functions of TXNIP are thioredoxin-dependent. It is also unclear whether TXNIP binding can inhibit glucose transporters without endocytosis. TXNIP-regulated control of ER stress should also be investigated further. . 38, 442-460.

Citing Articles

Oxidative Stress and the NLRP3 Inflammasome: Focus on Female Fertility and Reproductive Health.

Moustakli E, Stavros S, Katopodis P, Skentou C, Potiris A, Panagopoulos P Cells. 2025; 14(1.

PMID: 39791737 PMC: 11720220. DOI: 10.3390/cells14010036.

Sotorasib inhibits ubiquitination degradation of TXNIP and suppresses glucose metabolism in mutant bladder cancer.

Zhang Z, Liu M, Ji Y, Xiao D, Wang W, Zhou X Am J Cancer Res. 2024; 14(11):5251-5268.

PMID: 39659927 PMC: 11626273. DOI: 10.62347/XEBR7848.

DPEP Inhibits Cancer Cell Glucose Uptake, Glycolysis and Survival by Upregulating Tumor Suppressor TXNIP.

Zhou Q, Nguyen T, Mun J, Siegelin M, Greene L Cells. 2024; 13(12.

PMID: 38920655 PMC: 11201471. DOI: 10.3390/cells13121025.

References

Minn A, Hafele C, Shalev A . Thioredoxin-interacting protein is stimulated by glucose through a carbohydrate response element and induces beta-cell apoptosis. Endocrinology. 2005; 146(5):2397-405. DOI: 10.1210/en.2004-1378. View

Shalev A . Lack of TXNIP protects beta-cells against glucotoxicity. Biochem Soc Trans. 2008; 36(Pt 5):963-5. DOI: 10.1042/BST0360963. View

Batista T, Dagdeviren S, Carroll S, Cai W, Melnik V, Noh H . Arrestin domain-containing 3 (Arrdc3) modulates insulin action and glucose metabolism in liver. Proc Natl Acad Sci U S A. 2020; 117(12):6733-6740. PMC: 7104271. DOI: 10.1073/pnas.1922370117. View

Patwari P, Emilsson V, Schadt E, Chutkow W, Lee S, Marsili A . The arrestin domain-containing 3 protein regulates body mass and energy expenditure. Cell Metab. 2011; 14(5):671-83. PMC: 3216113. DOI: 10.1016/j.cmet.2011.08.011. View

Lee K, Kang H, Jeon J, Kim E, Yoon S, Song H . VDUP1 is required for the development of natural killer cells. Immunity. 2005; 22(2):195-208. DOI: 10.1016/j.immuni.2004.12.012. View

Souza de Lima D, Ogusku M, Sadahiro A, Pontillo A . Inflammasome genetics contributes to the development and control of active pulmonary tuberculosis. Infect Genet Evol. 2016; 41:240-244. DOI: 10.1016/j.meegid.2016.04.015. View

Hwang J, Suh H, Jeon Y, Hwang E, Nguyen L, Yeom J . The structural basis for the negative regulation of thioredoxin by thioredoxin-interacting protein. Nat Commun. 2014; 5:2958. PMC: 3941024. DOI: 10.1038/ncomms3958. View

Benovic J, Kuhn H, Weyand I, CODINA J, Caron M, Lefkowitz R . Functional desensitization of the isolated beta-adrenergic receptor by the beta-adrenergic receptor kinase: potential role of an analog of the retinal protein arrestin (48-kDa protein). Proc Natl Acad Sci U S A. 1987; 84(24):8879-82. PMC: 299654. DOI: 10.1073/pnas.84.24.8879. View

Buettner G, Wagner B, Rodgers V . Quantitative redox biology: an approach to understand the role of reactive species in defining the cellular redox environment. Cell Biochem Biophys. 2011; 67(2):477-83. PMC: 3661692. DOI: 10.1007/s12013-011-9320-3. View

10.

Patwari P, Chutkow W, Cummings K, Verstraeten V, Lammerding J, Schreiter E . Thioredoxin-independent regulation of metabolism by the alpha-arrestin proteins. J Biol Chem. 2009; 284(37):24996-5003. PMC: 2757204. DOI: 10.1074/jbc.M109.018093. View

11.

Park J, Lee S, Woo G, Kwon H, Kim D . Downregulation of TXNIP leads to high proliferative activity and estrogen-dependent cell growth in breast cancer. Biochem Biophys Res Commun. 2018; 498(3):566-572. DOI: 10.1016/j.bbrc.2018.03.020. View

12.

Wang Y, De Keulenaer G, Lee R . Vitamin D(3)-up-regulated protein-1 is a stress-responsive gene that regulates cardiomyocyte viability through interaction with thioredoxin. J Biol Chem. 2002; 277(29):26496-500. DOI: 10.1074/jbc.M202133200. View

13.

Lewis C, Parker S, Fiske B, McCloskey D, Gui D, Green C . Tracing compartmentalized NADPH metabolism in the cytosol and mitochondria of mammalian cells. Mol Cell. 2014; 55(2):253-63. PMC: 4106038. DOI: 10.1016/j.molcel.2014.05.008. View

14.

Stoltzman C, Peterson C, Breen K, Muoio D, Billin A, Ayer D . Glucose sensing by MondoA:Mlx complexes: a role for hexokinases and direct regulation of thioredoxin-interacting protein expression. Proc Natl Acad Sci U S A. 2008; 105(19):6912-7. PMC: 2383952. DOI: 10.1073/pnas.0712199105. View

15.

Yoshioka J, Chutkow W, Lee S, Kim J, Yan J, Tian R . Deletion of thioredoxin-interacting protein in mice impairs mitochondrial function but protects the myocardium from ischemia-reperfusion injury. J Clin Invest. 2011; 122(1):267-79. PMC: 3248280. DOI: 10.1172/JCI44927. View

16.

Thielen L, Chen J, Jing G, Moukha-Chafiq O, Xu G, Jo S . Identification of an Anti-diabetic, Orally Available Small Molecule that Regulates TXNIP Expression and Glucagon Action. Cell Metab. 2020; 32(3):353-365.e8. PMC: 7501995. DOI: 10.1016/j.cmet.2020.07.002. View

17.

Yamawaki H, Haendeler J, Berk B . Thioredoxin: a key regulator of cardiovascular homeostasis. Circ Res. 2003; 93(11):1029-33. DOI: 10.1161/01.RES.0000102869.39150.23. View

18.

Mohamed I, Sarhan N, Eladl M, El-Remessy A, El-Sherbiny M . Deletion of Thioredoxin-interacting protein ameliorates high fat diet-induced non-alcoholic steatohepatitis through modulation of Toll-like receptor 2-NLRP3-inflammasome axis: Histological and immunohistochemical study. Acta Histochem. 2018; 120(3):242-254. DOI: 10.1016/j.acthis.2018.02.006. View

19.

Rogoff D, Black K, McMillan D, White P . Contribution of hexose-6-phosphate dehydrogenase to NADPH content and redox environment in the endoplasmic reticulum. Redox Rep. 2010; 15(2):64-70. PMC: 7067336. DOI: 10.1179/174329210X12650506623249. View

20.

Liu Q, Zuo R, Wang K, Nong F, Fu Y, Huang S . Oroxindin inhibits macrophage NLRP3 inflammasome activation in DSS-induced ulcerative colitis in mice via suppressing TXNIP-dependent NF-κB pathway. Acta Pharmacol Sin. 2020; 41(6):771-781. PMC: 7468572. DOI: 10.1038/s41401-019-0335-4. View