Department of Stem Cell and Regenerative Biology and the Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts, USA.
Van Andel Institute, Grand Rapids, Michigan, USA.
Antioxid Redox Signal. 2023 Feb;38(4-6):442-460. doi: 10.1089/ars.2022.0022.
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.
硫氧还蛋白相互作用蛋白（TXNIP）是阻滞折叠超家族的成员，具有重要的细胞功能，包括细胞运输、线粒体能量生成和蛋白质循环。它是唯一已知与硫氧还蛋白共价结合并在葡萄糖代谢、炎症、细胞凋亡和癌症中发挥作用的阻滞域蛋白。TXNIP-硫氧还蛋白复合物的晶体结构提供了有关这种迷人相互作用的详细信息。最近的研究表明，TXNIP 由内质网（ER）应激诱导，激活 NLR 家族富含吡喃结构域的 3（NLRP3）炎性体，并能调节细胞内葡萄糖的转运。现在描述了 TXNIP 在各种癌症类型中的肿瘤抑制作用和在果糖吸收中的作用。TXNIP 对氧化还原状态的影响比其与硫氧还蛋白的相互作用更为复杂。尚不完全清楚 TXNIP 的哪些功能依赖于硫氧还蛋白。也不清楚 TXNIP 结合是否可以在没有胞吞作用的情况下抑制葡萄糖转运体。还应进一步研究 TXNIP 调节的 ER 应激控制。[Curr Opin Struct Biol. 2019;56:38,442-460]。
