Secretion of thioredoxin by normal and neoplastic cells through a leaderless secretory pathway.
Thioredoxin, despite its function as an intracellular disulfide reducing enzyme and its lack of a signal sequence, has been found to play some roles extracellularly. Here we show that thioredoxin is actively secreted by a variety of normal and transformed cells, including fibroblasts, airway epithelial cells, and activated B and T lymphocytes. Neither brefeldin A nor dinitrophenol, two drugs that block transport through the exocytic pathway, inhibit secretion of thioredoxin, indicating that the latter does not follow the classical ER-Golgi route. The secretory mechanism for thioredoxin shares several features with the alternative pathway described for interleukin-1 beta, such as the potentiating effect on secretion of several unrelated drugs and the sensitivity to methylamine. However, unlike interleukin-1 beta, thioredoxin is not detected in membrane-bound compartments of secreting cells. In addition, when COS7 are transfected with plasmids encoding pro-interleukin-1 beta or thioredoxin, only the latter is detectable extracellularly.
Rubartelli
A
A
Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
Bajetto
A
A
Allavena
G
G
Wollman
E
E
Sitia
R
R
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000502:physiology; D020126:Brefeldin A; D002460:Cell Line; D002478:Cells, Cultured; D003517:Cyclopentanes / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004926:Escherichia coli; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000378:metabolism; D013539:Simian virus 40 / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
D003517:Cyclopentanes; D007375:Interleukin-1; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D020126:Brefeldin A; D013879:Thioredoxins; D007770:L-Lactate Dehydrogenase