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2017 ; 2017
(ä): 8475125
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Cell Signaling with Extracellular Thioredoxin and Thioredoxin-Like Proteins:
Insight into Their Mechanisms of Action
#MMPMID29138681
Léveillard T
; Aït-Ali N
Oxid Med Cell Longev
2017[]; 2017
(ä): 8475125
PMID29138681
show ga
Thioredoxins are small thiol-oxidoreductase enzymes that control cellular redox
homeostasis. Paradoxically, human thioredoxin (TXN1) was first identified as the
adult T cell leukemia-derived factor (ADF), a secreted protein. ADF has been
implicated in a wide variety of cell-to-cell communication systems acting as a
cytokine or a chemokine. TRX80 is a truncated TXN1 protein with cytokine
activity. The unconventional secretion mechanism of these extracellular
thioredoxins is unknown. The thioredoxin system is relying on glucose metabolism
through the pentose phosphate pathway that provides reducing power in the form of
NADPH, the cofactor of thioredoxin reductase (TXNRD). While a complete
extracellular TXN system is present in the blood in the form of circulating TXN1
and TXNDR1, the source of extracellular NADPH remains a mystery. In the absence
of redox regenerating capacity, extracellular thioredoxins may rather be
prooxidant agents. Rod-derived cone viability factor (RdCVF) is the product of
intron retention of the nucleoredoxin-like 1 (NXNL1) gene, a secreted truncated
thioredoxin-like protein. The other product encoded by the gene, RdCVFL, is an
enzymatically active thioredoxin. This is a very singular example of positive
feedback of a superthioredoxin system encoded by a single gene likely emerging
during evolution from metabolic constraints on redox signaling.