The role of the redox protein thioredoxin in cell growth and cancer.

TitleThe role of the redox protein thioredoxin in cell growth and cancer.
Publication TypeJournal Article
Year of Publication2000
AuthorsPowis G, Mustacich DJ, Coon A
JournalFree radical biology & medicine
Volume29
Issue3-4
Pagination312-22
Date Published2000 Aug
ISSN0891-5849
KeywordsAnimals, Antineoplastic Agents, Antioxidants, Apoptosis, Cell Division, Coenzymes, Drug Resistance, Neoplasm, Growth Substances, Humans, Neoplasms, Oxidation-Reduction, Thioredoxins, Transcription Factors
Abstract

The thioredoxins are ubiquitous proteins containing a conserved -Trp-Cys-Gly-Pro-Cys-Lys- redox catalytic site. Mammalian thioredoxin family members include thioredoxin-1 (Trx1), mitochondrial thioredoxin-2 (Trx2), and a larger thioredoxin-like protein, p32TrxL. Thioredoxin is reduced by NADPH and thioredoxin reductase and, in turn reduces oxidized cysteine groups on proteins. When thioredoxin levels are elevated there is increased cell growth and resistance to the normal mechanism of programmed cell death. An increase in thioredoxin levels seen in many human primary cancers compared to normal tissue appears to contribute to increased cancer cell growth and resistance to chemotherapy. Mechanisms by which thioredoxin increases cell growth include an increased supply of reducing equivalents for DNA synthesis, activation of transcription factors that regulate cell growth, and an increase in the sensitivity of cells to other cytokines and growth factors. The mechanisms for the inhibition of apoptosis by thioredoxin are just now being elucidated. Because of its role in stimulating cancer cell growth and as an inhibitor of apoptosis, thioredoxin offers a target for the development of drugs to treat and prevent cancer.

Alternate JournalFree Radic. Biol. Med.