Ubiquitomics: An Overview and Future
Abstract
:1. Ubiquitous and Complex
2. Mapping Ubiquitination Sites on Protein Substrates
3. Lessons from Ubiquitin Site Profiling
4. Limitations of Ubiquitin Site Profiling
5. Proteomics with Activity-Based Probe Profiling
6. Ubiquitin Chain Topology and the Ubiquitin Code Hypothesis
7. Translational Ubiquitomics
8. Discussion
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Aim | Sample Requirement | Enrichment Method | MS Factors and Analysis | Example |
---|---|---|---|---|
Deep ubiquitome | Up to 50 mg cell culture | UbiSite | Prefractionation to increase depth | [21] |
Multiple PTMs | 1–20 mg cell culture | UbiSite or K-GG with additional PTM pulldowns | Multi-Omic data analysis | [31] |
Multiple conditions | 0.5–20 mg cell culture | K-GG or TUBE | Use of SILAC or TMT— in-solution or on-bead | [19,29] |
Chain type specific | 1–200 mg cell culture/yeast | TUBE, possible to combine with K-GG | - | [38] |
Low abundance modifications | <1 mg lysate | K-GG | Use of DIA to increase MS sensitivity | [22,23] |
Databases | Information | Reference |
---|---|---|
PhosphositePlus Database | Most comprehensive database for protein ubiquitination including most recent studies | [24] |
Protein Lysine Modification Database (PLMD) | Contains information on lysine ubiquitination and on other lysine modifications. Potential for investigating PTM crosstalk | [41] |
Mammalian Ubiquitination Site Database (mUbiSiDa) | A database of ubiquitination sites assembled in 2013 | [44] |
Ubiquitin and Ubiquitin-like conjugation Database (UUCD) | A database of actual and predicted ubiquitin and Ubl associated machinery in several species | [45] |
Ubiquitin Modifying Enzyme | Study Details | Reference |
---|---|---|
Cullin Ring Ligases | K-GG, CRL inhibition | [18] |
SPOP | K-GG, SILAC, mutant and overexpression | [33] |
Parkin | K-GG, inactive mutant | [28] |
K-GG, inactive mutant | [32] | |
LZTR1 | K-GG, knockout | [63] |
HUWE1 | K-GG, knockdown | [64] |
Skp2 | TUBE, overexpression | [65] |
USP7 | K-GG, DIA-MS, inhibitor | [23] |
USP9X | K-GG, knockdown | [66] |
USP22 | K-GG, knockdown and overexpression | [67] |
USP30 | K-GG, knockdown | [68] |
K-GG, knockout | [32] | |
K-GG, inhibitor | [69] | |
K-GG, knockout and inhibitor | [70] | |
USP32 | TUBE, knockdown | [71] |
Stimulus | ||
UV-induced DNA damage | K-GG, SILAC | [27] |
UV- and radiation-induced DNA damage | K-GG, SILAC | [31] |
TNF signalling | K-GG, SILAC | [72] |
Cell cycle synchronisation | K-GG, DIA-MS | [23] |
Lenalidomide treatment | K-GG, UbiFast/TMT | [29] |
CRP-XL signalling | K-GG | [73] |
Photosensitiser treatment | K-GG | [74] |
Proteasome inhibition | K-GG, SILAC | [18] |
K-GG, SILAC | [75] | |
UbiSite | [21] | |
Muscle atrophy | K-GG, time course examining mouse muscle ubiquitome following atrophy | [76] |
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Vere, G.; Kealy, R.; Kessler, B.M.; Pinto-Fernandez, A. Ubiquitomics: An Overview and Future. Biomolecules 2020, 10, 1453. https://doi.org/10.3390/biom10101453
Vere G, Kealy R, Kessler BM, Pinto-Fernandez A. Ubiquitomics: An Overview and Future. Biomolecules. 2020; 10(10):1453. https://doi.org/10.3390/biom10101453
Chicago/Turabian StyleVere, George, Rachel Kealy, Benedikt M. Kessler, and Adan Pinto-Fernandez. 2020. "Ubiquitomics: An Overview and Future" Biomolecules 10, no. 10: 1453. https://doi.org/10.3390/biom10101453
APA StyleVere, G., Kealy, R., Kessler, B. M., & Pinto-Fernandez, A. (2020). Ubiquitomics: An Overview and Future. Biomolecules, 10(10), 1453. https://doi.org/10.3390/biom10101453