Thioredoxin

Thioredoxin is a class of small is_associated_with::redox is_associated_with::proteins known to be present in all is_associated_with::organisms. It plays a role in many important is_associated_with::biological processes, including is_associated_with::redox signaling. In humans, it is encoded by the TXN is_associated_with::gene. is_associated_with::Loss-of-function mutation of either of the two human thioredoxin genes is lethal at the four-cell stage of the developing is_associated_with::embryo. Although not entirely understood, thioredoxin plays a central role in humans and is increasingly linked to medicine through their response to is_associated_with::reactive oxygen species (ROS). In is_associated_with::plants, thioredoxins regulate a spectrum of critical functions, ranging from photosynthesis to growth, flowering and the development and germination of seeds. It has also recently been found to play a role in cell-to-cell communication.

Function
Thioredoxins are is_associated_with::proteins that act as antioxidants by facilitating the reduction of other proteins by is_associated_with::cysteine thiol-disulfide exchange. Thioredoxins are found in nearly all known organisms and are essential for life in is_associated_with::mammals.

Thioredoxin is a 12-kD oxidoreductase enzyme containing a dithiol-disulfide active site. It is ubiquitous and found in many organisms from plants and bacteria to mammals. Multiple in vitro substrates for thioredoxin have been identified, including is_associated_with::ribonuclease, choriogonadotropins, coagulation factors, glucocorticoid receptor, and insulin. Reduction of insulin is classically used as an activity test.

Thioredoxins are characterized at the level of their is_associated_with::amino acid sequence by the presence of two vicinal cysteines in a CXXC motif. These two cysteines are the key to the ability of thioredoxin to reduce other proteins. Thioredoxin proteins also have a characteristic is_associated_with::tertiary structure termed the is_associated_with::thioredoxin fold.

The thioredoxins are kept in the reduced state by the flavoenzyme is_associated_with::thioredoxin reductase, in a NADPH-dependent reaction. Thioredoxins act as electron donors to is_associated_with::peroxidases and is_associated_with::ribonucleotide reductase. The related is_associated_with::glutaredoxins share many of the functions of thioredoxins, but are reduced by is_associated_with::glutathione rather than a specific reductase.

The benefit of thioredoxins to reduce is_associated_with::oxidative stress is shown by transgenic mice that overexpress thioredoxin, are more resistant to inflammation, and live 35% longer &mdash; supporting the free radical theory of aging. However, the controls of this study were short lived, which may have contributed to the apparent increase in longevity.

is_associated_with::Plants have an unusually complex complement of Trxs composed of six well-defined types (Trxs f, m, x, y, h, and o) that reside in different is_associated_with::cell compartments and function in an array of processes. In 2010 it was discovered for the first time that thioredoxin proteins are able to move from cell to cell, representing a novel form of cellular communication in plants.

Interactions
Thioredoxin has been shown to interact with:
 * is_associated_with::ASK1,
 * is_associated_with::Collagen, type I, alpha 1,
 * is_associated_with::Glucocorticoid receptor,
 * is_associated_with::SENP1, and
 * is_associated_with::TXNIP.