title: Thioredoxin is required for S-nitrosation of procaspase-3 and the inhibition of apoptosis in Jurkat cells.
abstract: S-nitrosation is a posttranslational, oxidative addition of NO to cysteine residues of proteins that has been proposed as a cGMP-independent signaling pathway [Hess DT, Matsumoto A, Kim SO, Marshall HE, Stamler JS (2005) Nat Rev Mol Cell Biol 6:150-166]. A paradox of S-nitrosation is that only a small set of reactive cysteines are modified in vivo despite the promiscuous reactivity NO exhibits with thiols, precluding the reaction of free NO as the primary mechanism of S-nitrosation. Here we show that a specific transnitrosation reaction between procaspase-3 and thioredoxin-1 (Trx) occurs in cultured human T cells and prevents apoptosis. Trx participation in catalyzing transnitrosation reactions in cells may be general because this protein has numerous protein-protein interactions and plays a key role in cellular redox homeostasis [Powis G, Montfort WR (2001) Annu Rev Pharmacol Toxicol 41:261-295], nitrosothiol content in cells [Haendeler J, Hoffmann J, Tischler V, Berk BC, Zeiher AM, Dimmeler S (2002) Nat Cell Biol 4:743-749], and antiapoptotic signaling.
authors.affiliation: Department of Chemistry, Lawrence Berkeley National Laboratory, University of California, Berkeley, CA 94720-1460, USA.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Mitchell
authors.forename: Sarah U
authors.initials: SU
authors.lastname: Morton
authors.forename: Nathaniel B
authors.initials: NB
authors.lastname: Fernhoff
authors.forename: Michael A
authors.initials: MA
authors.lastname: Marletta
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism* / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism*; D004792:Enzyme Precursors / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D009566:Nitrates / Q000378:metabolism*; D015538:Nitrosation; D015398:Signal Transduction / Q000502:physiology; D013379:Substrate Specificity; D013879:Thioredoxins / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D051017:Apoptosis Regulatory Proteins; D004792:Enzyme Precursors; D009566:Nitrates; C491203:TXN protein, human; D013879:Thioredoxins; D053148:Caspase 3