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Systematic and Quantitative Assessment of the Ubiquitin-Modified Proteome
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Summary Despite the diverse biological pathways known to be regulated by ubiquitylation, global identification of substrates that are targeted for ubiquitylation has remained a challenge. To globally characterize the ubiquitin-modified proteome (ubiquitinome), we utilized a monoclonal antibody that recognizes diglycine (diGly) containing isopeptides following trypsin digestion. We identify ~19,000 diGly modified lysine residues within ~ 5000 proteins. Using quantitative proteomics we monitored temporal changes in diGly site abundance in response to both proteasomal and translational inhibition indicating both a dependence of on-going translation to observe alterations in site abundance and distinct dynamics of individual modified lysines in response to proteasome inhibition. Further, we demonstrate that quantitative diGly proteomics can be utilized to identify substrates for cullin-RING ubiquitin ligases. Interrogation of the ubiquitinome allows for not only a quantitative assessment of alterations in protein homeostasis fidelity, but also identification of substrates for individual ubiquitin pathway enzymes.
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Cites
Protein Misfolding, Functional Amyloid, and Human Disease
Chiti, F., & Dobson, C. M. (2006) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.75.101304.123901 · Cited by 6,423
Lysine acetylation targets protein complexes and co-regulates major cellular functions
Choudhary, C., Kumar, C., Gnad, F., Nielsen, M. L., Rehman, M., Walther, T. C., Olsen, J. V., & Mann, M. (2009) · Science · doi:10.1126/science.1175371 · Cited by 4,040
An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer
Soucy, T. A., Smith, P. G., Milhollen, M. A., Berger, A. J., Gavin, J. M., Adhikari, S., Brownell, J. E., Burke, K. E., Cardin, D. P., Critchley, S., et al. (2009) · Nature · doi:10.1038/nature07884 · Cited by 1,990
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
Self-citationA proteomics approach to understanding protein ubiquitination
Peng, J., Schwartz, D., Elias, J. E., Thoreen, C. C., Cheng, D., Marsischky, G., Roelofs, J., Finley, D., & Gygi, S. P. (2003) · Nature Biotechnology · doi:10.1038/nbt849 · Cited by 1,602
Self-citationBeausoleil, S. A., Villén, J., Gerber, S. A., Rush, J., & Gygi, S. P. (2006) · Nature Biotechnology · doi:10.1038/nbt1240 · Cited by 1,577
Self-citationRapid degradation of a large fraction of newly synthesized proteins by proteasomes
Schubert, U., Antón, L. C., Gibbs, J., Norbury, C. C., Yewdell, J. W., & Bennink, J. R. (2000) · Nature · doi:10.1038/35008096 · Cited by 1,536
Quantitative Phosphoproteomics Reveals Widespread Full Phosphorylation Site Occupancy During Mitosis
Olsen, J. V., Vermeulen, M., Santamaria, A., Kumar, C., Miller, M. L., Jensen, L. J., Gnad, F., Cox, J., Jensen, T. S., Nigg, E. A., et al. (2010) · Science Signaling · doi:10.1126/scisignal.2000475 · Cited by 1,479
Xu, P., Duong, D. M., Seyfried, N. T., Cheng, D., Xie, Y., Robert, J., Rush, J., Hochstrasser, M., Finley, D., & Peng, J. (2009) · Cell · doi:10.1016/j.cell.2009.01.041 · Cited by 1,136
Self-citationBuilding ubiquitin chains: E2 enzymes at work
Ye, Y., & Rape, M. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2780 · Cited by 989
Schwartz, D., & Gygi, S. P. (2005) · Nature Biotechnology · doi:10.1038/nbt1146 · Cited by 879
Self-citationThe emerging complexity of protein ubiquitination
Komander, D. (2009) · Biochemical Society Transactions · doi:10.1042/bst0370937 · Cited by 821
Amyloid-like Aggregates Sequester Numerous Metastable Proteins with Essential Cellular Functions
Olzscha, H., Schermann, S. M., Woerner, A. C., Pinkert, S., Hecht, M. H., Tartaglia, G. G., Vendruscolo, M., Hayer-Hartl, M., Hartl, F. U., & Vabulas, R. M. (2011) · Cell · doi:10.1016/j.cell.2010.11.050 · Cited by 692
Ubiquitin-like protein conjugation and the ubiquitin–proteasome system as drug targets
Bedford, L., Lowe, J., Dick, L. R., Mayer, R. J., & Brownell, J. E. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3321 · Cited by 563 · cited 2×
“Further, there is widespread interest in targeting enzymes within the UPS to treat human disease (Bedford et al., 2011; Cohen and Tcherpakov, 2010), and an evaluation of the diGly-modified proteome under physiological dosing concentrations and schedules for these drugs may reveal useful endogenous biomarkers to interr…”
Ubiquitin Chain Editing Revealed by Polyubiquitin Linkage-Specific Antibodies
Newton, K., Matsumoto, M. L., Wertz, I. E., Kirkpatrick, D. S., Lill, J. R., Tan, J., Dugger, D., Gordon, N., Sidhu, S. S., Fellouse, F. A., et al. (2008) · Cell · doi:10.1016/j.cell.2008.07.039 · Cited by 555
Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling
Xu, G., Paige, J. S., & Jaffrey, S. R. (2010) · Nature Biotechnology · doi:10.1038/nbt.1654 · Cited by 534
Global changes to the ubiquitin system in Huntington's disease
Bennett, E. J., Shaler, T. A., Woodman, B., Ryu, K.-Y., Zaitseva, T. S., Becker, C. H., Bates, G. P., Schulman, H., & Kopito, R. R. (2007) · Nature · doi:10.1038/nature06022 · Cited by 497
Self-citationDynamics of Cullin-RING Ubiquitin Ligase Network Revealed by Systematic Quantitative Proteomics
Bennett, E. J., Rush, J., Gygi, S. P., & Harper, J. W. (2010) · Cell · doi:10.1016/j.cell.2010.11.017 · Cited by 386
Self-citationProtein Synthesis upon Acute Nutrient Restriction Relies on Proteasome Function
Vabulas, R. M., & Hartl, F. U. (2005) · Science · doi:10.1126/science.1121925 · Cited by 336
A Tandem Affinity Tag for Two-step Purification under Fully Denaturing Conditions
Tagwerker, C., Flick, K., Cui, M., Guerrero, C., Dou, Y., Auer, B., Baldi, P., Huang, L., & Kaiser, P. (2006) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m500368-mcp200 · Cited by 336
Mass Spectrometric Analysis of Lysine Ubiquitylation Reveals Promiscuity at Site Level
Danielsen, J. M. R., Sylvestersen, K. B., Bekker-Jensen, S., Szklarczyk, D., Poulsen, J. W., Horn, H., Jensen, L. J., Mailand, N., & Nielsen, M. L. (2011) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m110.003590 · Cited by 318
Will the Ubiquitin System Furnish as Many Drug Targets as Protein Kinases?
Cohen, P., & Tcherpakov, M. (2010) · Cell · doi:10.1016/j.cell.2010.11.016 · Cited by 271
A dynamic ubiquitin equilibrium couples proteasomal activity to chromatin remodeling
Dantuma, N. P., Groothuis, T. A. M., Salomons, F. A., & Neefjes, J. (2006) · The Journal of Cell Biology · doi:10.1083/jcb.200510071 · Cited by 265
Emerging Role of ISG15 in Antiviral Immunity
Skaug, B., & Chen, Z. J. (2010) · Cell · doi:10.1016/j.cell.2010.09.033 · Cited by 222
The DRiP hypothesis decennial: support, controversy, refinement and extension
Yewdell, J. W., & Nicchitta, C. V. (2006) · Trends in Immunology · doi:10.1016/j.it.2006.06.008 · Cited by 218
Whitby, F. G., Xia, G., Pickart, C. M., & Hill, C. P. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.52.34983 · Cited by 209
Identification of SCF Ubiquitin Ligase Substrates by Global Protein Stability Profiling
Yen, H.-C. S., & Elledge, S. J. (2008) · Science · doi:10.1126/science.1160462 · Cited by 208
Quantitative Analysis of global Ubiquitination in HeLa Cells by Mass Spectrometry
Meierhofer, D., Wang, X., Huang, L., & Kaiser, P. (2008) · Journal of Proteome Research · doi:10.1021/pr800468j · Cited by 194
Large‐scale analysis of the human ubiquitin‐related proteome
Matsumoto, M., Hatakeyama, S., Oyamada, K., Oda, Y., Nishimura, T., & Nakayama, K. I. (2005) · PROTEOMICS · doi:10.1002/pmic.200401280 · Cited by 177
Ribosomal proteins are targets for the NEDD8 pathway
Xirodimas, D. P., Sundqvist, A., Nakamura, A., Shen, L., Botting, C., & Hay, R. T. (2008) · EMBO reports · doi:10.1038/embor.2008.10 · Cited by 175
Mimnaugh, E. G., Chen, H. Y., Davie, J. R., Celis, J. E., & Neckers, L. (1997) · Biochemistry · doi:10.1021/bi970998j · Cited by 169
A Targeted Proteomic Analysis of the Ubiquitin-Like Modifier Nedd8 and Associated Proteins
Jones, J., Wu, K., Yang, Y., Guerrero, C., Nillegoda, N., Pan, Z.-Q., & Huang, L. (2008) · Journal of Proteome Research · doi:10.1021/pr700749v · Cited by 163
Liao, H., Liu, X. J., Blank, J. L., Bouck, D. C., Bernard, H., Garcia, K., & Lightcap, E. S. (2011) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m111.009183 · Cited by 67
Lessons from interconnected ubiquitylation and acetylation of p53: think metastable networks
Benkirane, M., Sardet, C., & Coux, O. (2010) · Biochemical Society Transactions · doi:10.1042/bst0380098 · Cited by 24
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Komander, D., & Rape, M. (2012) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060310-170328 · Cited by 3,679
Swatek, K. N., & Komander, D. (2016) · Cell Research · doi:10.1038/cr.2016.39 · Cited by 2,081
Hornbeck, P. V., Kornhauser, J. M., Tkachev, S., Zhang, B., Skrzypek, E., Murray, B., Latham, V., & Sullivan, M. (2012) · Nucleic Acids Research · doi:10.1093/nar/gkr1122 · Cited by 1,646
The increasing complexity of the ubiquitin code
Yau, R., & Rape, M. (2016) · Nature Cell Biology · doi:10.1038/ncb3358 · Cited by 1,054
Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization
Sarraf, S. A., Raman, M., Guarani-Pereira, V., Sowa, M. E., Huttlin, E. L., Gygi, S. P., & Harper, J. W. (2013) · Nature · doi:10.1038/nature12043 · Cited by 1,010
Self-citation
Metadata
- Authors
- Kim, W., Bennett, E. J., Huttlin, E. L., Guo, A., Li, J., Possemato, A., Sowa, M. E., Rad, R., Rush, J., Comb, M. J., Harper, J. W., & Gygi, S. P.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2011-10
- Volume
- 44
- Issue
- 2
- Pages
- 325-340
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2143538182
- Cited by
- 1,613
- References
- 34
- FWCI
- 45.14
- Type
- journal article
- Language
- en
- Open access
- bronze
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