Various regulation of adult T cell leukemia-derived factor (ADF)/human thioredoxin expression and its cytoprotective action

Many agents which induce apoptosis are either oxidants or stimulators of cellular oxidative metabolism. Conversely, many inhibitors of apoptosis including ADF/human thioredoxin, have antioxidant activities or enhance cellular antioxidant defenses. Cells exist in a state of oxidative siege in which survival requires an appropriate balance of oxidants and antioxidants. Eukaryotic cells may benefit from this perilous existence by invoking oxidative stress as a common mediator of apoptosis. ATL-derived factor (ADF) was first defined as the IL-2 Rα-inducing factor produced by ATF cell lines. Subsequent purification and gene cloning of ADF proved that it is a human homologue of the bacterial coenzyme thioredoxin. ADF has strong thiol-related reducing activities and also has multiple functions on various cell types. In this article, we introduce recent findings concerning 1) cytoprotective function of ADF, especially the cytoprotective effect of ADF on thiol-depleted lymphocytes, 2) redox regulation of signal transduction especially of tyrosine phosphorylation, and 3) translocation of ADF/TRX in response to some stress. We would like to discuss the importance of this subject in basic and clinical medicine.