Redox regulation by thioredoxin superfamily; Protection against oxidative stress and aging

Thioredoxin (TRX) is a 12 kD protein with redox-active dithiol in the activ e site; -Cys-Gly-Pro-Cys-. We originally cloned human TRX as adult T cell l eukemia derived factor (ADF) produced by HTLV-I transformed cells. TRX and related molecules maintain a cellular reducing enviroment, working in conce rt with the glutathione system. Physiologically, TRX has cytoprotective eff ects against oxidative stress. TRX promotes DNA binding of transcription fa ctors such as NF-kB, AP-1, p53, and PEBP-2. The TRX superfamily, including thioredoxin-2 (mitochondrial thioredoxin) and glutaredoxin, are involved in biologically important phenomena via the redox-regulating system. Thioredo xin-binding protein-2, which we recently identified by a yeast two-hybrid s ystem, is a type of endogenous modulator of TRX activity. TRX is secreted f rom the cells and exhibits cytokine-like and chemokine-like activities. Red ox regulation by TRX plays a crucial role in biological responses against o xidative stress.