TY - JOUR
T1 - Thioredoxin is required for S-nitrosation of procaspase-3 and the inhibition of apoptosis in Jurkat cells
AU - Mitchell, Douglas A.
AU - Morton, Sarah U.
AU - Fernhoff, Nathaniel B.
AU - Marletta, Michael A.
PY - 2007/7/10
Y1 - 2007/7/10
N2 - 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.
AB - 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.
KW - Nitric oxide
KW - Programmed cell death
KW - S-nitrosylation
KW - Signal transduction
UR - http://www.scopus.com/inward/record.url?scp=34547427294&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34547427294&partnerID=8YFLogxK
U2 - 10.1073/pnas.0704898104
DO - 10.1073/pnas.0704898104
M3 - Article
C2 - 17606900
AN - SCOPUS:34547427294
SN - 0027-8424
VL - 104
SP - 11609
EP - 11614
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 28
ER -