Redox control of caspase-3 activity by thioredoxin and other reduced proteins.
Caspases are cysteine proteinases that play a critical role in the execution phase of apoptosis. The active site cysteine residue must be reduced for caspase activity. Thioredoxins are redox proteins that catalyze the reduction of cysteine residues. We have examined the ability of various recombinant human thioredoxins to activate caspase-3. The EC(50) for caspase-3 activation by reduced thioredoxin-1 was 2.5 microM, by reduced glutathione 1.0 mM and by dithiothreitol 3.5 mM. A catalytic site redox-inactive mutant thioredoxin-1 was almost as active as thioredoxin-1 in activating caspase-3. Caspase activation was shown to correlate with the number of reduced cysteine residues in the thioredoxins. Reduced insulin and serum albumin were as effective on a molar basis as thioredoxin-1 in activating caspase-3. Thus, caspase-3 activation is not a specific effect of thioredoxins but is a property shared by other reduced proteins.
Baker
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A
Arizona Cancer Center, University of Arizona, Tucson, Arizona, 85724-5024, USA.
Santos
B D
BD
Powis
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G
D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020134:Catalytic Domain / Q000235:genetics; D003545:Cysteine / Q000737:chemistry; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D009154:Mutation; D010084:Oxidation-Reduction; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D012709:Serum Albumin / Q000494:pharmacology; D013879:Thioredoxins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*
D007328:Insulin; D011994:Recombinant Proteins; D012709:Serum Albumin; D013879:Thioredoxins; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D003545:Cysteine