Redox Regulation by Thioredoxin and Thioredoxin‐Binding Proteins

Abstract

Recent works have shown the importance of reduction/oxidation (redox) regulation in various biological phenomena. Thioredoxin is a 12‐kDa protein with redox‐active dithiol in the active site ‐Cys‐Gly‐Pro‐Cys‐ and constitutes a major thiol reducing system, the thioredoxin system. Thioredoxin plays multiple roles in cellular processes such as proliferation or apoptosis. It also promotes DNA binding of transcription factors such as NF‐ κB, AP‐1, p53, and PEBP2. Overexpression of thioredoxin suppresses the degradation of I κB and the transactivation of NF‐ κB, whereas overexpression of nuclear‐targeted thioredoxin exhibits the enhancement of NF‐ κB‐dependent transactivation. ASK1, a MAP kinase kinase kinase mediating the TNF‐ α signal has been identified as a thioredoxin binding protein. Thioredoxin shows an inhibitory effect on the TNF‐ α induced activation of ASK1 and p38 MAP kinase pathway. We identified p40phox as the thioredoxin binding protein‐1 (TBP‐1) and vitamin D3 up‐regulated protein 1 (VDUP1) as the thioredoxin binding protein‐2 (TBP‐2) by yeast two‐hybrid system. TBP‐2/VDUP1 negatively regulates the expre and reducing activity of thioredoxin. Thioredoxin interacting proteins may be involved in thioredoxin‐mediating regulation.