Thiol redox transitions by thioredoxin and thioredoxin-binding protein-2 in cell signaling.
The cellular thiol redox state is a crucial mediator of metabolic, signaling and transcriptional processes in cells, and an exquisite balance between the oxidizing and reducing states is essential for the normal function and survival of cells. Reactive oxygen species (ROS) are widely known to function as a kind of second messenger for intracellular signaling and to modulate the thiol redox state. Thiol reduction is mainly controlled by the thioredoxin (TRX) system and glutathione (GSH) systems as scavengers of ROS and regulators of the protein redox states. The thioredoxin system is composed of several related molecules interacting through the cysteine residues at the active site, including thioredoxin, thioredoxin-2, a mitochondrial thioredoxin family, and transmembrane thioredoxin-related protein (TMX), an endoplasmic reticulum (ER)-specific thioredoxin family. Thioredoxin couples with thioredoxin-dependent peroxidases (peroxiredoxin) to scavenge hydrogen peroxide. In addition, thioredoxin does not simply act only as a scavenger of ROS but also as an important regulator of oxidative stress response through protein-protein interaction. The interaction of thioredoxin and thioredoxin-binding proteins such as thioredoxin-binding protein-2 (TBP-2, also called as Txnip or VDUP1), apoptosis signal kinase (ASK-1), redox factor 1 (Ref-1), Forkhead box class O 4 (FoxO4), and nod-like receptor proteins (NLRPs) suggested unconventional functions of thioredoxin and a novel mechanism of redox regulation. Here, we introduce the central mechanism of thiol redox transition in cell signaling regulated by thioredoxin and related molecules.
Yoshihara
Eiji
E
Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto, Japan.
Chen
Zhe
Z
Matsuo
Yoshiyuki
Y
Masutani
Hiroshi
H
Yodoi
Junji
J
D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D010084:Oxidation-Reduction; D015398:Signal Transduction; D013879:Thioredoxins / Q000737:chemistry* / Q000145:classification / Q000378:metabolism
D002352:Carrier Proteins; C486715:TXNIP protein, human; D013879:Thioredoxins