System-wide identification and prioritization of enzyme substrates by thermal analysis.

Carcinoma Drug Discovery Enzymes / chemistry HCT116 Cells Humans Mass Spectrometry Poly(ADP-ribose) Polymerases / chemistry Protein Processing, Post-Translational Proteins / chemistry Proteomics / methods Proto-Oncogene Proteins / chemistry Proto-Oncogene Proteins c-akt / chemistry Substrate Specificity Thioredoxin Reductase 1 / chemistry

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
26 02 2021
Historique:
received: 08 04 2020
accepted: 26 01 2021
entrez: 27 2 2021
pubmed: 28 2 2021
medline: 16 3 2021
Statut: epublish

Résumé

Despite the immense importance of enzyme-substrate reactions, there is a lack of general and unbiased tools for identifying and prioritizing substrate proteins that are modified by the enzyme on the structural level. Here we describe a high-throughput unbiased proteomics method called System-wide Identification and prioritization of Enzyme Substrates by Thermal Analysis (SIESTA). The approach assumes that the enzymatic post-translational modification of substrate proteins is likely to change their thermal stability. In our proof-of-concept studies, SIESTA successfully identifies several known and novel substrate candidates for selenoprotein thioredoxin reductase 1, protein kinase B (AKT1) and poly-(ADP-ribose) polymerase-10 systems. Wider application of SIESTA can enhance our understanding of the role of enzymes in homeostasis and disease, opening opportunities to investigate the effect of post-translational modifications on signal transduction and facilitate drug discovery.

Identifiants

DOI: 10.1038/s41467-021-21540-6 PMID: 33637753 PMC: PMC7910609
pubmed: 33637753
doi: 10.1038/s41467-021-21540-6
pii: 10.1038/s41467-021-21540-6
pmc: PMC7910609
doi:

Substances chimiques

Enzymes 0
Proteins 0
Proto-Oncogene Proteins 0
TXNRD1 protein, human EC 1.8.1.9
Thioredoxin Reductase 1 EC 1.8.1.9
PARP10 protein, human EC 2.4.2.30
Poly(ADP-ribose) Polymerases EC 2.4.2.30
Proto-Oncogene Proteins c-akt EC 2.7.11.1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1296

Références

Placzek, S. et al. BRENDA in 2017: New perspectives and new tools in BRENDA. Nucleic Acids Res. 41, D380–D388 (2017).
doi: 10.1093/nar/gkw952
Romero, P. et al. Computational prediction of human metabolic pathways from the complete human genome. Genome Biol. 6, R2 (2005).
pubmed: 15642094 doi: 10.1186/gb-2004-6-1-r2
Mann, M. & Jensen, O. N. Proteomic analysis of post-translational modifications. Nat. Biotechnol. 21, 255–261 (2003).
pubmed: 12610572 doi: 10.1038/nbt0303-255
Ochoa, D. et al. The functional landscape of the human phosphoproteome. Nat. Biotechnol. 38, 365–373 (2020).
pubmed: 31819260 doi: 10.1038/s41587-019-0344-3
Huang, J. X. et al. High throughput discovery of functional protein modifications by Hotspot Thermal Profiling. Nat. Methods 16, 894–901 (2019).
pubmed: 31384043 pmcid: 7238970 doi: 10.1038/s41592-019-0499-3
Beltrao, P. et al. Systematic functional prioritization of protein posttranslational modifications. Cell 150, 413–425 (2012).
pubmed: 22817900 pmcid: 3404735 doi: 10.1016/j.cell.2012.05.036
Wesche, H., Xiao, S.-H. & Young, S. W. High throughput screening for protein kinase inhibitors. Comb. Chem. High. Throughput Screen. 8, 181–195 (2005).
pubmed: 15777182 doi: 10.2174/1386207053258514
Lehel, C., Daniel-Issakani, S., Brasseur, M. & Strulovici, B. A chemiluminescent microtiter plate assay for sensitive detection of protein kinase activity. Anal. Biochem. 244, 340–346 (1997).
pubmed: 9025951 doi: 10.1006/abio.1996.9894
Steger, M. et al. Phosphoproteomics reveals that Parkinson’s disease kinase LRRK2 regulates a subset of Rab GTPases. Elife 5, e12813 (2016).
pubmed: 26824392 pmcid: 4769169 doi: 10.7554/eLife.12813
Byrd, K. M. & Blagg, B. S. J. Chaperone substrate provides missing link for cancer drug discovery. J. Biol. Chem. 293, 2381–2382 (2018).
pubmed: 29453286 pmcid: 5818199 doi: 10.1074/jbc.H118.001591
Yen, H. C. S. & Elledge, S. J. Identification of SCF ubiquitin ligase substrates by global protein stability profiling. Science 322, 923–929 (2008).
pubmed: 18988848 doi: 10.1126/science.1160462
Flint, A. J., Tiganis, T., Barford, D. & Tonks, N. K. Development of ‘substrate-trapping’ mutants to identify physiological substrates of protein tyrosine phosphatases. Proc. Natl Acad. Sci. USA 94, 1680–1685 (1997).
pubmed: 9050838 doi: 10.1073/pnas.94.5.1680 pmcid: 19976
Low, T. Y. et al. A systems-wide screen identifies substrates of the SCFβTrCP ubiquitin ligase. Sci. Signal. 7, rs8 (2014).
pubmed: 25515538 doi: 10.1126/scisignal.2005882
Köhn, M. et al. A microarray strategy for mapping the substrate specificity of protein tyrosine phosphatase. Angew. Chem. Int. Ed. 46, 7700–7703 (2007).
doi: 10.1002/anie.200701601
Feilner, T. et al. High throughput identification of potential Arabidopsis mitogen-activated protein kinases substrates. Mol. Cell. Proteom. 4, 1558–1568 (2005).
doi: 10.1074/mcp.M500007-MCP200
Ubersax, J. A. et al. Targets of the cyclin-dependent kinase Cdk1. Nature 425, 859–864 (2003).
pubmed: 14574415 doi: 10.1038/nature02062
Matsuoka, S. et al. ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science 316, 1160–1166 (2007).
pubmed: 17525332 doi: 10.1126/science.1140321
Anders, L. et al. A Systematic Screen for CDK4/6 Substrates Links FOXM1 Phosphorylation to Senescence Suppression in. Cancer Cells Cancer Cell 20, 620–634 (2011).
pubmed: 22094256 doi: 10.1016/j.ccr.2011.10.001
Molina, D. M. et al. Monitoring drug target engagement in cells and tissues using the cellular thermal shift assay. Science 341, 84–87 (2013).
doi: 10.1126/science.1233606
Savitski, M. M. et al. Tracking cancer drugs in living cells by thermal profiling of the proteome. Science 346, 1255784 (2014).
pubmed: 25278616 doi: 10.1126/science.1255784
Geer, M. A. & Fitzgerald, M. C. Characterization of the Saccharomyces cerevisiae ATP-Interactome using the iTRAQ-SPROX Technique. J. Am. Soc. Mass Spectrom. 27, 233–243 (2016).
pubmed: 26530046 doi: 10.1007/s13361-015-1290-z
Piazza, I. et al. A map of protein-metabolite interactions reveals principles of chemical communication. Cell 172, 358–372 (2018). e23.
pubmed: 29307493 doi: 10.1016/j.cell.2017.12.006
Dai, L. et al. Modulation of protein-interaction states through the cell cycle. Cell 173, 1481–1494 (2018). e13.
pubmed: 29706543 doi: 10.1016/j.cell.2018.03.065
Becher, I. et al. Pervasive protein thermal stability variation during the cell cycle. Cell 173, 1495–1507 (2018). e18.
pubmed: 29706546 pmcid: 5998384 doi: 10.1016/j.cell.2018.03.053
Drake, W. R., Hou, C.-W., Zachara, N. E. & Grimes, C. L. New use for CETSA: monitoring innate immune receptor stability via post-translational modification by OGT. J. Bioenerg. Biomembr. 50, 231–240 (2018).
pubmed: 29671171 pmcid: 6126917 doi: 10.1007/s10863-018-9754-z
Chernobrovkin, A., Marin-Vicente, C., Visa, N. & Zubarev, R. A. Functional Identification of Target by Expression Proteomics (FITExP) reveals protein targets and highlights mechanisms of action of small molecule drugs. Sci. Rep. 5, 11176 (2015).
pubmed: 26052917 pmcid: 4459150 doi: 10.1038/srep11176
Saei, A. A. et al. ProTargetMiner as a proteome signature library of anticancer molecules for functional discovery. Nat. Commun. 10, 5715 (2019).
pubmed: 31844049 pmcid: 6915695 doi: 10.1038/s41467-019-13582-8
Bylesjö, M. et al. OPLS discriminant analysis: combining the strengths of PLS‐DA and SIMCA classification. J. Chemom. A J. Chemom. Soc. 20, 341–351 (2006).
Arnér, E. S. J. & Holmgren, A. Physiological functions of thioredoxin and thioredoxin reductase. Eur. J. Biochem 267, 6102–6109 (2000).
pubmed: 11012661 doi: 10.1046/j.1432-1327.2000.01701.x
Galindo‐Prieto, B., Eriksson, L. & Trygg, J. Variable influence on projection (VIP) for orthogonal projections to latent structures (OPLS). J. Chemom. 28, 623–632 (2014).
doi: 10.1002/cem.2627
Triba, M. N. et al. PLS/OPLS models in metabolomics: the impact of permutation of dataset rows on the K-fold cross-validation quality parameters. Mol. Biosyst. 11, 13–19 (2015).
pubmed: 25382277 doi: 10.1039/C4MB00414K
Arnér, E. S. J. Focus on mammalian thioredoxin reductases—important selenoproteins with versatile functions. Biochim. Biophys. Acta. 1790, 495–526 (2009).
pubmed: 19364476 doi: 10.1016/j.bbagen.2009.01.014
Björnstedt, M., Xue, J., Huang, W., Akesson, B. & Holmgren, A. The thioredoxin and glutaredoxin systems are efficient electron donors to human plasma glutathione peroxidase. J. Biol. Chem. 269, 29382–29384 (1994).
pubmed: 7961915 doi: 10.1016/S0021-9258(18)43889-6
Jiménez, A., Pelto-Huikko, M., Gustafsson, J.-Å. & Miranda-Vizuete, A. Characterization of human thioredoxin-like-1: potential involvement in the cellular response against glucose deprivation. FEBS Lett. 580, 960–967 (2006).
pubmed: 16438969 doi: 10.1016/j.febslet.2006.01.025
Léveillard, T. & Aït-Ali, N. Cell signaling with extracellular thioredoxin and thioredoxin-like proteins: insight into their mechanisms of action. Oxid. Med. Cell. Longev. 2017 https://doi.org/10.1155/2017/8475125 (2017).
Franken, H. et al. Thermal proteome profiling for unbiased identification of direct and indirect drug targets using multiplexed quantitative mass spectrometry. Nat. Protoc. 10, 1567–1593 (2015).
pubmed: 26379230 doi: 10.1038/nprot.2015.101
Kamariah, N., Sek, M. F., Eisenhaber, B., Eisenhaber, F. & Grüber, G. Transition steps in peroxide reduction and a molecular switch for peroxide robustness of prokaryotic peroxiredoxins. Sci. Rep. 6, 1–15 (2016).
doi: 10.1038/srep37610
Su, H. P. et al. Identification and characterization of a dimerization domain in CED-6, an adapter protein involved in engulfment of apoptotic cells. J. Biol. Chem. 275, 9542–9549 (2000).
doi: 10.1074/jbc.275.13.9542 pubmed: 10734103
Pader, I. et al. Thioredoxin-related protein of 14 kDa is an efficient L-cystine reductase and S-denitrosylase. Proc. Natl Acad. Sci. 111, 6964–6969 (2014).
pubmed: 24778250 doi: 10.1073/pnas.1317320111 pmcid: 4024855
Lundstrom, J. & Holmgren, A. Protein disulfide-isomerase is a substrate for thioredoxin reductase and has thioredoxin-like activity. J. Biol. Chem. 265, 9114–9120 (1990).
pubmed: 2188973 doi: 10.1016/S0021-9258(19)38819-2
Sridharan, S. et al. Proteome-wide solubility and thermal stability profiling reveals distinct regulatory roles for ATP. Nat. Commun. 10, 1155 (2019).
pubmed: 30858367 pmcid: 6411743 doi: 10.1038/s41467-019-09107-y
Wang, V. Y. F. et al. Bcl3 phosphorylation by Akt, Erk2, and IKK is required for its transcriptional activity. Mol. Cell 67, 484–497 (2017).
pubmed: 28689659 pmcid: 6571149 doi: 10.1016/j.molcel.2017.06.011
Amano, M. et al. Kinase-interacting substrate screening is a novel method to identify kinase substrates. J. Cell Biol. 209, 895–912 (2015).
pubmed: 26101221 pmcid: 4477863 doi: 10.1083/jcb.201412008
Xue, L. & Tao, W. A. Current technologies to identify protein kinase substrates in high throughput. Front. Biol. 8, 216–227 (2013).
doi: 10.1007/s11515-013-1257-z
Wu, X. et al. Activation of diverse signalling pathways by oncogenic PIK3CA mutations. Nat. Commun. 5, 1–13 (2014).
doi: 10.1038/ncomms5961
Lee, M. Y. et al. Endothelial Akt1 mediates angiogenesis by phosphorylating multiple angiogenic substrates. Proc. Natl Acad. Sci. 111, 12865–12870 (2014).
pubmed: 25136137 doi: 10.1073/pnas.1408472111 pmcid: 4156707
Hornbeck, P. V. et al. PhosphoSitePlus: a comprehensive resource for investigating the structure and function of experimentally determined post-translational modifications in man and mouse. Nucleic Acids Res 40, D261–D270 (2012).
pubmed: 22135298 doi: 10.1093/nar/gkr1122
Potel, C. M. et al. Impact of phosphorylation on thermal stability of proteins. bioRxiv https://doi.org/10.1101/2020.01.14.903849 (2020).
Smith, I. R. et al. Identification of phosphosites that alter protein thermal stability. bioRxiv https://doi.org/10.1101/2020.01.14.904300 (2020).
Matsuda-Lennikov, M. et al. Lysosomal interaction of Akt with Phafin2: a critical step in the induction of autophagy. PLoS One 9, e79795 (2014).
pubmed: 24416124 pmcid: 3885392 doi: 10.1371/journal.pone.0079795
Kleine, H. et al. Substrate-assisted catalysis by PARP10 limits its activity to mono-ADP-ribosylation. Mol. Cell 32, 57–69 (2008).
pubmed: 18851833 doi: 10.1016/j.molcel.2008.08.009
Martello, R. et al. Proteome-wide identification of the endogenous ADP-ribosylome of mammalian cells and tissue. Nat. Commun. 7, 1–13 (2016).
doi: 10.1038/ncomms12917
Carter-O’Connell, I., Jin, H., Morgan, R. K., David, L. L. & Cohen, M. S. Engineering the substrate specificity of ADP-ribosyltransferases for identifying direct protein targets. J. Am. Chem. Soc. 136, 5201–5204 (2014).
pubmed: 24641686 pmcid: 4445677 doi: 10.1021/ja412897a
Carter-O’Connell, I. et al. Identifying family-member-specific targets of mono-ARTDs by using a chemical genetics approach. Cell Rep. 14, 621–631 (2016).
pubmed: 26774478 pmcid: 5423403 doi: 10.1016/j.celrep.2015.12.045
Mayo, E. et al. ARTD10/PARP10 induces ADP-ribosylation of GAPDH and recruits GAPDH into cytosolic membrane-free cell bodies when overexpressed in mammalian. Cells Chall. 9, 22 (2018).
Herzog, N. et al. Caspase‐dependent cleavage of the mono‐ADP‐ribosyltransferase ARTD 10 interferes with its pro‐apoptotic function. FEBS J. 280, 1330–1343 (2013).
pubmed: 23305266 doi: 10.1111/febs.12124
Vaidya, S., Velázquez-Delgado, E. M., Abbruzzese, G. & Hardy, J. A. Substrate-induced conformational changes occur in all cleaved forms of caspase-6. J. Mol. Biol. 406, 75–91 (2011).
pubmed: 21111746 doi: 10.1016/j.jmb.2010.11.031
Qiao, M. et al. Mst1 is an interacting protein that mediates PHLPPs’ induced apoptosis. Mol. Cell 38, 512–523 (2010).
pubmed: 20513427 doi: 10.1016/j.molcel.2010.03.017
Arroyo, R. et al. Systematic identification of molecular links between core and candidate genes in breast cancer. J. Mol. Biol. 427, 1436–1450 (2015).
pubmed: 25640309 doi: 10.1016/j.jmb.2015.01.014
Lee, W. P. et al. Akt phosphorylates myc-associated zinc finger protein (MAZ), releases P-MAZ from the p53 promoter, and activates p53 transcription. Cancer Lett. 375, 9–19 (2016).
pubmed: 26902421 doi: 10.1016/j.canlet.2016.02.023
Zhang, X., Lu, X., Akhter, S., Georgescu, M. M. & Legerski, R. J. FANCI is a negative regulator of Akt activation. Cell Cycle 15, 1134–1143 (2016).
pubmed: 27097374 pmcid: 4889286 doi: 10.1080/15384101.2016.1158375
Reinhard, F. B. M. et al. Thermal proteome profiling monitors ligand interactions with cellular membrane proteins. Nat. Methods 12, 1129–1131 (2015).
pubmed: 26524241 doi: 10.1038/nmeth.3652
Gaetani, M. et al. Proteome integral solubility alteration: a high-throughput proteomics assay for target deconvolution. J. Proteome Res. 18, 4027–4037 (2019).
pubmed: 31545609 doi: 10.1021/acs.jproteome.9b00500
Garrigue-Antar, L., Hartigan, N. & Kadler, K. E. Post-translational modification of bone morphogenetic protein-1 is required for secretion and stability of the protein. J. Biol. Chem. 277, 43327–43334 (2002).
pubmed: 12218058 doi: 10.1074/jbc.M207342200
Price, J. L. et al. Context-dependent effects of asparagine glycosylation on Pin WW folding kinetics and thermodynamics. J. Am. Chem. Soc. 132, 15359–15367 (2010).
pubmed: 20936810 pmcid: 2965790 doi: 10.1021/ja106896t
Kim, Y. H. et al. Deamidation, but not truncation, decreases the urea stability of a lens structural protein, βB1-crystallin. Biochemistry 41, 14076–14084 (2002).
pubmed: 12437365 doi: 10.1021/bi026288h
Culyba, E. K. et al. Protein native-state stabilization by placing aromatic side chains in N-glycosylated reverse turns. Science 331, 571–575 (2011).
pubmed: 21292975 pmcid: 3099596 doi: 10.1126/science.1198461
Gavrilov, Y., Shental-Bechor, D., Greenblatt, H. M. & Levy, Y. Glycosylation may reduce protein thermodynamic stability by inducing a conformational distortion. J. Phys. Chem. Lett. 6, 3572–3577 (2015).
pubmed: 26722726 doi: 10.1021/acs.jpclett.5b01588
Hebert, D. N., Lamriben, L., Powers, E. T. & Kelly, J. W. The intrinsic and extrinsic effects of N-linked glycans on glycoproteostasis. Nat. Chem. Biol. 10, 902–910 (2014).
pubmed: 25325701 pmcid: 4232232 doi: 10.1038/nchembio.1651
Shental-Bechor, D. & Levy, Y. Effect of glycosylation on protein folding: a close look at thermodynamic stabilization. Proc. Natl Acad. Sci. 105, 8256–8261 (2008).
pubmed: 18550810 doi: 10.1073/pnas.0801340105 pmcid: 2448824
Takata, T., Oxford, J. T., Brandon, T. R. & Lampi, K. J. Deamidation alters the structure and decreases the stability of human lens βΑ3-crystallin. Biochemistry 46, 8861–8871 (2007).
pubmed: 17616172 doi: 10.1021/bi700487q
Sun, W. et al. Monitoring structural modulation of redox-sensitive proteins in cells with MS-CETSA. Redox Biol. 24, 101168 (2019).
pubmed: 30925293 pmcid: 6439307 doi: 10.1016/j.redox.2019.101168
Saei, A. A. et al. Comprehensive chemical proteomics for target deconvolution of the redox active drug auranofin. Redox Biol. 32, 101491 (2020).
pubmed: 32199331 pmcid: 7082630 doi: 10.1016/j.redox.2020.101491
Cheng, Q. & Arnér, E. S. J. Selenocysteine insertion at a predefined UAG codon in a Release Factor 1 (RF1)-depleted Escherichia coli host strain bypasses species barriers in recombinant selenoprotein translation. J. Biol. Chem. 292, 5476–5487 (2017).
pubmed: 28193838 pmcid: 5392690 doi: 10.1074/jbc.M117.776310
Thorsell, A.-G. et al. Structural basis for potency and promiscuity in poly (ADP-ribose) polymerase (PARP) and tankyrase inhibitors. J. Med. Chem. 60, 1262–1271 (2017).
pubmed: 28001384 doi: 10.1021/acs.jmedchem.6b00990
Saei, A. A. et al. SIESTA as a universal unbiased proteomics approach for identification and prioritization of enzyme substrates. Protoc. Exch. https://doi.org/10.21203/rs.3.pex-1327/v1 (2021).
Li, J. et al. TMTpro reagents: a set of isobaric labeling mass tags enables simultaneous proteome-wide measurements across 16 samples. Nat. Methods 17, 399–404 (2020).
pubmed: 32203386 doi: 10.1038/s41592-020-0781-4 pmcid: 7302421
Cox, J. & Mann, M. MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat. Biotechnol. 26, 1367–1372 (2008).
pubmed: 19029910 doi: 10.1038/nbt.1511
Szklarczyk, D. et al. The STRING database in 2017: quality-controlled protein–protein association networks, made broadly accessible. Nucleic Acids Res 45, D362–D368 (2016).
pubmed: 27924014 pmcid: 5210637 doi: 10.1093/nar/gkw937
Vizcaíno, J. A. et al. ProteomeXchange provides globally coordinated proteomics data submission and dissemination. Nat. Biotechnol. 32, 223–226 (2014).
pubmed: 24727771 pmcid: 3986813 doi: 10.1038/nbt.2839

Auteurs

Amir Ata Saei (AA)

Division of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden. Amirata.Saei.Dibavar@ki.se.
Department of Cell Biology, Harvard Medical School, Boston, MA, USA. Amirata.Saei.Dibavar@ki.se.
ORCID: 0000-0002-2639-6328

Christian M Beusch (CM)

Division of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
ORCID: 0000-0001-9100-8283

Pierre Sabatier (P)

Division of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
ORCID: 0000-0002-2734-1791

Juan Astorga Wells (JA)

Division of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
ORCID: 0000-0003-1017-8841

Hassan Gharibi (H)

Division of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
ORCID: 0000-0002-3072-4929

Zhaowei Meng (Z)

Division of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.

Alexey Chernobrovkin (A)

Division of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Pelago Bioscience AB, Solna, Sweden.
ORCID: 0000-0001-7709-0161

Sergey Rodin (S)

Division of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.

Katja Näreoja (K)

Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.

Ann-Gerd Thorsell (AG)

Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.

Tobias Karlberg (T)

Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.

Qing Cheng (Q)

Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.

Susanna L Lundström (SL)

Division of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.

Massimiliano Gaetani (M)

Division of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
SciLifeLab, Stockholm, Sweden.
Chemical Proteomics Core Facility, Division of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
ORCID: 0000-0001-5610-0797

Ákos Végvári (Á)

Division of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Proteomics Biomedicum, Division of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
ORCID: 0000-0002-1287-0906

Elias S J Arnér (ESJ)

Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
ORCID: 0000-0002-4807-6114

Herwig Schüler (H)

Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
ORCID: 0000-0003-4059-3501

Roman A Zubarev (RA)

Division of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden. Roman.Zubarev@ki.se.
Department of Pharmacological & Technological Chemistry, I.M. Sechenov First Moscow State Medical University, Moscow, Russia. Roman.Zubarev@ki.se.
ORCID: 0000-0001-9839-2089

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Classifications MeSH

questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs épithéliales épidermoïdes et glandulaires › Carcinomes › System-wide identification and prioritization...
questionsmedicales.fr › Techniques d'investigation › Développement de médicament › Découverte de médicament › System-wide identification and prioritization...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › System-wide identification and prioritization...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Cellules HCT116 › System-wide identification and prioritization...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › System-wide identification and prioritization...
questionsmedicales.fr › Techniques d'investigation › Techniques de chimie analytique › Spectrométrie de masse › System-wide identification and prioritization...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › Glycosyltransferase › Pentosyltransferases › ADP ribose transferases › Poly(ADP-ribose) polymerases › System-wide identification and prioritization...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Modification traductionnelle des protéines › Maturation post-traductionnelle des protéines › System-wide identification and prioritization...
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