Nishiyama A, Masutani H, Nakamura H, Nishinaka Y, Yodoi J
Department of Biological Responses, Institute for Virus Research, Kyoto University, Japan.
IUBMB Life. 2001 Jul;52(1-2):29-33. doi: 10.1080/15216540252774739.
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.
近期研究表明，还原/氧化（redox）调节在各种生物学现象中具有重要意义。硫氧还蛋白是一种12 kDa的蛋白质，其活性位点含有具有氧化还原活性的二硫醇-Cys-Gly-Pro-Cys-，并构成主要的硫醇还原系统——硫氧还蛋白系统。硫氧还蛋白在细胞增殖或凋亡等细胞过程中发挥多种作用。它还能促进转录因子如核因子κB（NF-κB）、激活蛋白-1（AP-1）、p53和PEBP2与DNA的结合。硫氧还蛋白的过表达可抑制IκB的降解和NF-κB的反式激活，而核靶向硫氧还蛋白的过表达则表现出NF-κB依赖性反式激活的增强。ASK1是一种介导肿瘤坏死因子-α（TNF-α）信号的丝裂原活化蛋白激酶激酶激酶，已被鉴定为硫氧还蛋白结合蛋白。硫氧还蛋白对TNF-α诱导的ASK1激活和p38丝裂原活化蛋白激酶途径具有抑制作用。我们通过酵母双杂交系统鉴定出p40phox为硫氧还蛋白结合蛋白-1（TBP-1），维生素D3上调蛋白1（VDUP1）为硫氧还蛋白结合蛋白-2（TBP-2）。TBP-2/VDUP1负向调节硫氧还蛋白的表达和还原活性。硫氧还蛋白相互作用蛋白可能参与硫氧还蛋白介导的氧化还原调节。
