Redox regulation by thioredoxin superfamily; protection against oxidative stress and aging.
Thioredoxin (TRX) is a 12 kD protein with redox-active dithiol in the active site; -Cys-Gly-Pro-Cys-. We originally cloned human TRX as adult T cell leukemia derived factor (ADF) produced by HTLV-I transformed cells. TRX and related molecules maintain a cellular reducing enviroment, working in concert with the glutathione system. Physiologically, TRX has cytoprotective effects against oxidative stress. TRX promotes DNA binding of transcription factors 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. Thioredoxin-binding protein-2, which we recently identified by a yeast two-hybrid system, is a type of endogenous modulator of TRX activity. TRX is secreted from the cells and exhibits cytokine-like and chemokine-like activities. Redox regulation by TRX plays a crucial role in biological responses against oxidative stress.
Department of Biological Responses, Institute for virus Research, Kyoto University, Sakyo, Japan.
T
T
Tanaka
H
H
Nakamura
A
A
Nishiyama
F
F
Hosoi
H
H
Masutani
H
H
Wada
J
J
Yodoi
D000375:Aging; D000818:Animals; D004247:DNA / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D013879:Thioredoxins / Q000378:metabolism* / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism
D014157:Transcription Factors; D013879:Thioredoxins; D004247:DNA