Redox regulation by thioredoxin and thioredoxin-binding proteins.
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-kappaB, AP-1, p53, and PEBP2. Overexpression of thioredoxin suppresses the degradation of IkappaB and the transactivation of NF-kappaB, whereas overexpression of nuclear-targeted thioredoxin exhibits the enhancement of NF-kappaB-dependent transactivation. ASK1, a MAP kinase kinase kinase mediating the TNF-alpha signal has been identified as a thioredoxin binding protein. Thioredoxin shows an inhibitory effect on the TNF-alpha 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 expression and reducing activity of thioredoxin. Thioredoxin interacting proteins may be involved in thioredoxin-mediating redox regulation.
Nishiyama
A
A
Department of Biological Responses, Institute for Virus Research, Kyoto University, Japan.
Masutani
H
H
Nakamura
H
H
Nishinaka
Y
Y
Yodoi
J
J
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002451:Cell Compartmentation; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D009685:Nuclear Envelope / Q000378:metabolism; D010084:Oxidation-Reduction; D011485:Protein Binding; D013879:Thioredoxins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
D002352:Carrier Proteins; D014157:Transcription Factors; D013879:Thioredoxins