The mammalian thioredoxins are a family of small (approximately 12 kDa) red
ox proteins that undergo NADPH-dependent reduction by thioredoxin reductase
and in turn reduce oxidized cysteine groups on proteins. The two main thio
redoxins are thioredoxin-l, a cytosolic and nuclear form, and thioredoxin-2
, a mitochondrial form. Thioredoxin-1 has been studied more. It performs ma
ny biological actions including the supply of reducing equivalents to thior
edoxin peroxidases and ribonucleotide reductase, the regulation of transcri
ption factor activity, and the regulation of enzyme activity by heterodimer
formation. Thioredoxin-l stimulates cell growth and is an inhibitor of apo
ptosis. Thioredoxins may play a role in a variety of human diseases includi
ng cancer. An increased level of thioredoxin-l is found in many human tumor
s, where it is associated with aggressive tumor growth. Drugs are being dev
eloped that inhibit thioredoxin and that have antitumor activity.