The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
Site-Specific Proteomic Mapping Identifies Selectively Modified Regulatory Cysteine Residues in Functionally Distinct Protein Networks
Open accessAbstract
S-Acylation, S-glutathionylation, S-nitrosylation, and S-sulfenylation are prominent, chemically distinct modifications that regulate protein function, redox sensing, and trafficking. Although the biological significance of these modifications is increasingly appreciated, their integration in the proteome remains unknown. Novel mass spectrometry-based technologies identified 2,596 predominately unique sites in 1,319 mouse liver proteins under physiological conditions. Structural analysis localized the modifications in unique, evolutionary conserved protein segments, outside commonly annotated functional regions. Contrary to expectations, propensity for modification did not correlate with biophysical properties that regulate cysteine reactivity. However, the in vivo chemical reactivity is fine-tuned for specificity, demonstrated by the nominal complementation between the four modifications and quantitative proteomics which showed that a reduction in S-nitrosylation is not correlated with increased S-glutathionylation. A comprehensive survey uncovered clustering of modifications within biologically related protein networks. The data provide the first evidence for the occurrence of distinct, endogenous protein networks that undergo redox signaling through specific cysteine modifications.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Recent studies of the proteome of eNOS−/− mice compared with wild type mice identify a more limited set of S-nitrosated proteins (125, 378).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [378]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Structure, mechanism and regulation of peroxiredoxins
Wood, Z. A., Schröder, E., Harris, J. R., & Poole, L. B. (2003) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(02)00003-8 · Cited by 2,546
Signal transduction by reactive oxygen species
Finkel, T. (2011) · Journal of Cell Biology · doi:10.1083/jcb.201102095 · Cited by 2,322
A tissue-specific atlas of mouse protein phosphorylation and expression
Huttlin, E. L., Jedrychowski, M. P., Elias, J. E., Goswami, T., Rad, R., Beausoleil, S. A., Villén, J., Haas, W., Sowa, M. E., & Gygi, S. P. (2010) · Cell · doi:10.1016/j.cell.2010.12.001 · Cited by 1,778
Quantitative reactivity profiling predicts functional cysteines in proteomes
Weerapana, E., Wang, C., Simon, G. M., Richter, F., Khare, S., Dillon, M. B. D., Bachovchin, D. A., Mowen, K., Baker, D., & Cravatt, B. F. (2010) · Nature · doi:10.1038/nature09472 · Cited by 1,684
Denu, J. M., & Tanner, K. G. (1998) · Biochemistry · doi:10.1021/bi973035t · Cited by 945
Hydrogen Sulfide-Linked Sulfhydration of NF-κB Mediates Its Antiapoptotic Actions
Sen, N., Paul, B. D., Gadalla, M. M., Mustafa, A. K., Sen, T., Xu, R., Kim, S., & Snyder, S. H. (2012) · Molecular Cell · doi:10.1016/j.molcel.2011.10.021 · Cited by 733
Krüger, M., Moser, M., Ussar, S., Thievessen, I., Luber, C. A., Forner, F., Schmidt, S., Zanivan, S., Fässler, R., & Mann, M. (2008) · Cell · doi:10.1016/j.cell.2008.05.033 · Cited by 680
Integrated proteomic analysis of post-translational modifications by serial enrichment
Mertins, P., Qiao, J., Patel, J., Udeshi, N. D., Clauser, K. R., Mani, D. R., Burgess, M. W., Gillette, M. A., Jaffe, J. D., & Carr, S. A. (2013) · Nature Methods · doi:10.1038/nmeth.2518 · Cited by 619
Cardioprotection by S-nitrosation of a cysteine switch on mitochondrial complex I
Chouchani, E. T., Methner, C., Nadtochiy, S. M., Logan, A., Pell, V. R., Ding, S., James, A. M., Cochemé, H. M., Reinhold, J., Lilley, K. S., et al. (2013) · Nature Medicine · doi:10.1038/nm.3212 · Cited by 619 · cited 1×
“Combined with the abundance of SNO proteins within cluster 2, which is highly populated with mitochondria localization and oxidoreductase activities, this fits well with the known cardioprotective effects of SNOduring ischemia and the role of SNO in fatty acid b-oxidation (Chouchani et al., 2013; Doulias et al., 2013b…”
BackgroundS-glutathionylation in protein redox regulation
Dalle‐Donne, I., Rossi, R., Giustarini, D., Colombo, R., & Milzani, A. (2007) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.06.014 · Cited by 506
Peroxide-dependent sulfenylation of the EGFR catalytic site enhances kinase activity
Paulsen, C. E., Truong, T. H., García, F., Homann, A., Gupta, V., Leonard, S. E., & Carroll, K. S. (2011) · Nature Chemical Biology · doi:10.1038/nchembio.736 · Cited by 484
Self-citationKislinger, T., Cox, B., Kannan, A., Chung, C., Hu, P., Ignatchenko, A., Scott, M. S., Gramolini, A. O., Morris, Q., Hallett, M. T., et al. (2006) · Cell · doi:10.1016/j.cell.2006.01.044 · Cited by 482
Quantifying the global cellular thiol–disulfide status
Hansen, R. E., Roth, D., & Winther, J. R. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812149106 · Cited by 437
Marino, S. M., & Gladyshev, V. N. (2010) · Journal of Molecular Biology · doi:10.1016/j.jmb.2010.09.027 · Cited by 401
Self-citationThiol-based redox switches in eukaryotic proteins
Brandes, N., Schmitt, S., & Jakob, U. (2009) · Antioxidants & Redox Signaling · doi:10.1089/ars.2008.2285 · Cited by 373
Global profiling of dynamic protein palmitoylation
Martin, B. R., Wang, C., Adibekian, A., Tully, S. E., & Cravatt, B. F. (2011) · Nature Methods · doi:10.1038/nmeth.1769 · Cited by 370
Schmidt, B., Ho, L., & Hogg, P. J. (2006) · Biochemistry · doi:10.1021/bi0603064 · Cited by 342
Getting into position: the catalytic mechanisms of protein ubiquitylation
Passmore, L. A., & Barford, D. (2004) · Biochemical Journal · doi:10.1042/bj20040198 · Cited by 315
Lind, C., Gerdes, R. G., Hamnell-Pamment, Y., Schuppe‐Koistinen, I., von Löwenhielm, H. B., Holmgren, A., & Cotgreave, I. A. (2002) · Archives of Biochemistry and Biophysics · doi:10.1016/s0003-9861(02)00468-x · Cited by 311
Novel Role for Glutathione S-Transferase π
Townsend, D. M., Manevich, Y., He, L., Hutchens, S., Pazoles, C. J., & Tew, K. D. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m805586200 · Cited by 307
Thioredoxin catalyzes the S-nitrosation of the caspase-3 active site cysteine
Mitchell, D. A., & Marletta, M. A. (2005) · Nature Chemical Biology · doi:10.1038/nchembio720 · Cited by 298
Mechanisms of S-nitrosothiol formation and selectivity in nitric oxide signaling
Smith, B. C., & Marletta, M. A. (2012) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2012.10.016 · Cited by 279
Analysis and Functional Prediction of Reactive Cysteine Residues
Marino, S. M., & Gladyshev, V. N. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.r111.275578 · Cited by 278
Self-citationZinc-Binding Cysteines: Diverse Functions and Structural Motifs
Pace, N., & Weerapana, E. (2014) · Biomolecules · doi:10.3390/biom4020419 · Cited by 258
Doulias, P., Greene, J. L., Greco, T. M., Τενοπούλου, Μ., Seeholzer, S. H., Dunbrack, R. L., & Ischiropoulos, H. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1008036107 · Cited by 256
Self-citationDoulias, P.-T., Tenopoulou, M., Greene, J. L., Raju, K., & Ischiropoulos, H. (2013) · Science Signaling · doi:10.1126/scisignal.2003252 · Cited by 250
Self-citationGroitl, B., & Jakob, U. (2014) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2014.03.007 · Cited by 245
Marino, S. M., & Gladyshev, V. N. (2009) · Journal of Molecular Biology · doi:10.1016/j.jmb.2009.10.042 · Cited by 215
Self-citationS-Glutathionylation of Cryptic Cysteines Enhances Titin Elasticity by Blocking Protein Folding
Alegre‐Cebollada, J., Kosuri, P., Giganti, D. O., Eckels, E. C., Rivas‐Pardo, J. A., Hamdani, N., Warren, C. M., Solaro, R. J., Linke, W. A., & Fernández, J. M. (2014) · Cell · doi:10.1016/j.cell.2014.01.056 · Cited by 204
Martı́nez-Ruiz, A., & Lamas, S. (2007) · Cardiovascular Research · doi:10.1016/j.cardiores.2007.03.016 · Cited by 202
New Insights into the Mechanisms of Protein Palmitoylation
Linder, M. E., & Deschenes, R. J. (2003) · Biochemistry · doi:10.1021/bi034159a · Cited by 202
Global proteomic assessment of the classical protein-tyrosine phosphatome and “Redoxome”
Karisch, R., Fernandez, M., Taylor, P., Virtanen, C., St-Germain, J. R., Jin, L. L., Harris, I. S., Mori, J., Mak, T. W., Senis, Y. A., et al. (2011) · Cell · doi:10.1016/j.cell.2011.07.020 · Cited by 179
Endogenous Protein S-Nitrosylation in E. coli : Regulation by OxyR
Seth, D., Hausladen, A., Wang, Y.-J., & Stamler, J. S. (2012) · Science · doi:10.1126/science.1215643 · Cited by 158
Nitric Oxide Inhibits c-Jun DNA Binding by Specifically TargetedS-Glutathionylation
Klatt, P., Pineda‐Molina, E., & Lamas, S. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.22.15857 · Cited by 157
Salsbury, F. R., Knutson, S. T., Poole, L. B., & Fetrow, J. S. (2008) · Protein Science · doi:10.1110/ps.073096508 · Cited by 125
Identification of S-Nitrosylated Targets of Thioredoxin Using a Quantitative Proteomic Approach
Benhar, M., Thompson, J. W., Moseley, M. A., & Stamler, J. S. (2010) · Biochemistry · doi:10.1021/bi100619k · Cited by 115
The Local Electrostatic Environment Determines Cysteine Reactivity of Tubulin
Britto, P. J., Knipling, L., & Wolff, J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204263200 · Cited by 108
Selective irreversible inhibition of a protease by targeting a noncatalytic cysteine
Hagel, M., Niu, D., St Martin, T., Sheets, M. P., Qiao, L., Bernard, H., Karp, R. M., Zhu, Z., Labenski, M. T., Chaturvedi, P., et al. (2011) · Nature Chemical Biology · doi:10.1038/nchembio.492 · Cited by 95
Determination of site-specificity of S-glutathionylated cellular proteins
Hamnell-Pamment, Y., Lind, C., Palmberg, C., Bergman, T., & Cotgreave, I. A. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.04.130 · Cited by 73
Conway, M. E., Poole, L. B., & Hutson, S. M. (2004) · Biochemistry · doi:10.1021/bi0498050 · Cited by 68
Verification of automated peptide identifications from proteomic tandem mass spectra
Tabb, D. L., Friedman, D. B., & Ham, A. L. (2006) · Nature Protocols · doi:10.1038/nprot.2006.330 · Cited by 59
Shi, Y., Tang, W., Hao, S., & Wang, C. (2005) · Biochemistry · doi:10.1021/bi0480943 · Cited by 42
A Low pK Cysteine at the Active Site of Mouse Methionine Sulfoxide Reductase A
Lim, J. C., Gruschus, J. M., Kim, G., Berlett, B. S., Tjandra, N., & Levine, R. L. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.369116 · Cited by 34
Proteomic analysis of peptides tagged with dimedone and related probes
Martínez-Acedo, P., Gupta, V., & Carroll, K. S. (2014) · Journal of Mass Spectrometry · doi:10.1002/jms.3336 · Cited by 31
Self-citationDoulias, P., Raju, K., Greene, J. L., Τενοπούλου, Μ., & Ischiropoulos, H. (2012) · Methods · doi:10.1016/j.ymeth.2012.10.009 · Cited by 25
Self-citationReactive Cysteine in the Structural Zn2+ Site of the C1B Domain from PKCα
Stewart, M. D., & Igumenova, T. I. (2012) · Biochemistry · doi:10.1021/bi300750w · Cited by 22
Flagged first, then by citations
Cited by
Sorted by citations
Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation
Tejero, J., Shiva, S., & Gladwin, M. T. (2019) · Physiological Reviews · doi:10.1152/physrev.00036.2017 · Cited by 541
Sulfhydryl groups as targets of mercury toxicity
Ajsuvakova, O. P., Tinkov, A. A., Aschner, M., da Rocha, J. B. T., Michalke, B., Геннадиевна, С. М., Skalny, A. V., Butnariu, M., Dadar, M., Sărac, I., et al. (2020) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2020.213343 · Cited by 384
Stomberski, C. T., Hess, D. T., & Stamler, J. S. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7403 · Cited by 297
Chemical proteomics reveals new targets of cysteine sulfinic acid reductase
Akter, S., Fu, L., Jung, Y., Conte, M. L., Lawson, J. R., Lowther, W. T., Sun, R., Liu, K., Yang, J. H., & Carroll, K. S. (2018) · Nature Chemical Biology · doi:10.1038/s41589-018-0116-2 · Cited by 235
Self-citationCysteine Sulfenylation Directs IRE-1 to Activate the SKN-1/Nrf2 Antioxidant Response
Hourihan, J. M., Mazzeo, L. E. M., Fernández-Cárdenas, L. P., & Blackwell, T. K. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.07.019 · Cited by 209
Metadata
- Authors
- Gould, N. S., Evans, P., Martínez-Acedo, P., Marino, S. M., Gladyshev, V. N., Carroll, K. S., & Ischiropoulos, H.
- Affiliations
- Children's Hospital of Philadelphia (US)
- Scripps Research Institute (US)
- Akdeniz University (TR)
- Brigham and Women's Hospital (US)
- Corresponding author
- Ischiropoulos, Harry
- Venue
- Chemistry & Biology
- Publisher
- Elsevier BV
- Published
- 2015-07
- Volume
- 22
- Issue
- 7
- Pages
- 965-975
- ISSN
- 1074-5521 (ISSN-L)
- PMC
- PMC4515171
- OpenAlex
- W1867506901
- Cited by
- 128
- References
- 46
- Citations by year
- 2026: 2 · 2025: 11 · 2024: 11 · 2023: 11 · 2022: 10 · 2021: 12 · 2020: 12 · 2019: 9 · 2018: 17 · 2017: 14 · 2016: 14 · 2015: 5
- FWCI
- 7.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Chemistry & Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL54926, R01HL054926)
- National Cancer Institute (R01CA174864, CA174986)
- National Institute of General Medical Sciences (GM 065204, R37GM065204, GM102187, R01GM065204, R01GM102187)
- National Institute of Environmental Health Sciences (P30ES013508)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD086984)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- cysteine modification, S-acylation, S-glutathionylation, S-nitrosylation, redox signaling, protein networks, post-translational modification
- MeSH terms
- Amino Acid Sequence, Animals, Cysteine, Humans, Models, Molecular, Molecular Sequence Data, Peptide Mapping, Protein Processing, Post-Translational, Mass Spectrometry, Proteome, Proteomics, Mice, Protein Interaction Maps
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
