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Science 23 April 1999:
Vol. 284. no. 5414, pp. 651 - 654
DOI: 10.1126/science.284.5414.651
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Reports

Fas-Induced Caspase Denitrosylation

Joan B. Mannick, 1* Alfred Hausladen, 2 Limin Liu, 3 Douglas T. Hess, 2 Ming Zeng, 2 Qian X. Miao, 1 Laurie S. Kane, 2 Andrew J. Gow, 2 Jonathan S. Stamler 23*

Only a few intracellular S-nitrosylated proteins have been identified, and it is unknown if protein S-nitrosylation/denitrosylation is a component of signal transduction cascades. Caspase-3 zymogens were found to be S-nitrosylated on their catalytic-site cysteine in unstimulated human cell lines and denitrosylated upon activation of the Fas apoptotic pathway. Decreased caspase-3 S-nitrosylation was associated with an increase in intracellular caspase activity. Fas therefore activates caspase-3 not only by inducing the cleavage of the caspase zymogen to its active subunits, but also by stimulating the denitrosylation of its active-site thiol. Protein S-nitrosylation/denitrosylation can thus serve as a regulatory process in signal transduction pathways.

1 Department of Adult Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
2 Department of Medicine, Divisions of Respiratory and Cardiovascular Medicine and Department of Cell Biology, and
3 Howard Hughes Medical Institute, Duke University Medical Center, Box 2612, 321 MSRB, Durham, NC 27710, USA.
*   To whom correspondence should be addressed. E-mail: (J.S.S.) staml001{at}mc.duke.edu and (J.B.M.) Joan_mannick{at}dfci.harvard.edu

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K. Fang, R. Johns, T. Macdonald, M. Kinter, and B. Gaston (2000)
Am J Physiol Lung Cell Mol Physiol 279, L716-L721
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cGMP-independent inotropic effects of nitric oxide and peroxynitrite donors: potential role for nitrosylation.
N. Paolocci, U. E. G. Ekelund, T. Isoda, M. Ozaki, K. Vandegaer, D. Georgakopoulos, R. W. Harrison, D. A. Kass, and J. M. Hare (2000)
Am J Physiol Heart Circ Physiol 279, H1982-H1988
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Nitric oxide inhibits calpain-mediated proteolysis of talin in skeletal muscle cells.
T. J. Koh and J. G. Tidball (2000)
Am J Physiol Cell Physiol 279, C806-C812
   Abstract »    Full Text »    PDF »
Mechanisms of the pro- and anti-oxidant actions of nitric oxide in atherosclerosis.
R. P. Patel, A.-L. Levonen, J. H. Crawford, and V. M. Darley-Usmar (2000)
Cardiovasc Res 47, 465-474
   Abstract »    Full Text »    PDF »
Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens.
C. Nathan and M. U. Shiloh (2000)
PNAS 97, 8841-8848
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Nitric Oxide Induces Thymocyte Apoptosis Via a Caspase-1-Dependent Mechanism.
X. Zhou, S. A. Gordon, Y.-M. Kim, R. A. Hoffman, Y. Chen, X.-R. Zhang, R. L. Simmons, and H. R. Ford (2000)
J. Immunol. 165, 1252-1258
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Ascorbic Acid and Glutathione Modulate the Biological Activity of S-Nitrosoglutathione.
A. Xu, J. A. Vita, and J. F. Keaney Jr (2000)
Hypertension 36, 291-295
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Oxygen-Glucose Deprivation Induces Inducible Nitric Oxide Synthase and Nitrotyrosine Expression in Cerebral Endothelial Cells Editorial Comment.
J. Xu, L. He, S. H. Ahmed, S.-W. Chen, M. P. Goldberg, J. S. Beckman, C. Y. Hsu, and C. Iadecola (2000)
Stroke 31, 1744-1751
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Adrenomedullin and Nitric Oxide Inhibit Human Endothelial Cell Apoptosis via a Cyclic GMP-Independent Mechanism.
M. Sata, M. Kakoki, D. Nagata, H. Nishimatsu, E. Suzuki, T. Aoyagi, S. Sugiura, H. Kojima, T. Nagano, K. Kangawa, et al. (2000)
Hypertension 36, 83-88
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Two distinct mechanisms of nitric oxide-mediated neuronal cell death show thiol dependency.
A. J. Gow, Q. Chen, M. Gole, M. Themistocleous, V. M.-Y. Lee, and H. Ischiropoulos (2000)
Am J Physiol Cell Physiol 278, C1099-C1107
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Activation of Calpain I Converts Excitotoxic Neuron Death into a Caspase-independent Cell Death.
S. Lankiewicz, C. Marc Luetjens, N. Truc Bui, A. J. Krohn, M. Poppe, G. M. Cole, T. C. Saido, and J. H. M. Prehn (2000)
J. Biol. Chem. 275, 17064-17071
   Abstract »    Full Text »    PDF »
Pharmacological frontiers in the treatment of AIDS dementia.
D. McGuire and K. Marder (2000)
J Psychopharmacol 14, 251-257
   Abstract »    PDF »


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