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

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, p32 TrxL. Thioredoxin is reduced by NADPH and...

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Bibliographic Details
Published in:Free radical biology & medicine 2000-08, Vol.29 (3), p.312-322
Main Authors: Powis, Garth, Mustacich, Debbie, Coon, Amy
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Antioxidants - chemistry
Antioxidants - metabolism
Apoptosis
Apoptosis - drug effects
Cancer
Cell Division - drug effects
Cell growth
Coenzymes - antagonists & inhibitors
Coenzymes - chemistry
Coenzymes - genetics
Coenzymes - metabolism
Drug Resistance, Neoplasm
Free radicals
Growth Substances - chemistry
Growth Substances - genetics
Growth Substances - metabolism
Humans
Neoplasms - metabolism
Neoplasms - pathology
Oxidation-Reduction
Redox control
Thioredoxin
Thioredoxins - antagonists & inhibitors
Thioredoxins - chemistry
Thioredoxins - genetics
Thioredoxins - metabolism
Transcription Factors - metabolism
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Summary: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, p32 TrxL. 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.
ISSN:0891-5849
1873-4596
DOI:10.1016/S0891-5849(00)00313-0