{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T21:06:13Z","timestamp":1760043973354},"reference-count":45,"publisher":"Informa UK Limited","issue":"11","license":[{"start":{"date-parts":[[2019,11,2]],"date-time":"2019-11-02T00:00:00Z","timestamp":1572652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":["www.tandfonline.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,11,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Protein\u2013protein interactions (PPIs) lead the formation of protein complexes that perform biochemical reactions that maintain the living state of the living cell. Although therapeutic drugs should influence the formation of protein complexes in addition to PPI network, the methodology analyzing such influences remain to be developed. Here, we demonstrate that a new approach combining HPLC (high performance liquid chromatography) for separating protein complexes, and the SILAC (stable isotope labeling using amino acids in cell culture) method for relative protein quantification, enable us to identify the protein complexes influenced by a drug. We applied this approach to the analysis of thalidomide action on HepG2 cells, assessed the identified proteins by clustering data analyses, and assigned 135 novel protein complexes affected by the drug. We propose that this approach is applicable to elucidating the mechanisms of actions of other therapeutic drugs on the PPI network, and the formation of protein complexes.<\/jats:p>","DOI":"10.1080\/09168451.2019.1637244","type":"journal-article","created":{"date-parts":[[2019,7,8]],"date-time":"2019-07-08T06:53:01Z","timestamp":1562568781000},"page":"2034-2048","update-policy":"http:\/\/dx.doi.org\/10.1080\/tandf_crossmark_01","source":"Crossref","is-referenced-by-count":3,"title":["New approach to evaluating the effects of a drug on protein complexes with quantitative proteomics, using the SILAC method and bioinformatic approach"],"prefix":"10.1080","volume":"83","author":[{"given":"Natsuki","family":"Kurokawa","sequence":"first","affiliation":[{"name":"Graduate School of Agriculture, Tokyo University of Agriculture & Technology, Fuchu-shi, Tokyo, Japan"},{"name":"Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, Chuo-ku, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taro","family":"Kishimoto","sequence":"additional","affiliation":[{"name":"Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, Chuo-ku, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kohei","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, Chuo-ku, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Kondo","sequence":"additional","affiliation":[{"name":"Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, Chuo-ku, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuhiro","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Graduate School of Agriculture, Tokyo University of Agriculture & Technology, Fuchu-shi, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yutaka","family":"Miura","sequence":"additional","affiliation":[{"name":"Graduate School of Agriculture, Tokyo University of Agriculture & Technology, Fuchu-shi, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"301","published-online":{"date-parts":[[2019,11,2]]},"reference":[{"issue":"1","key":"2021033115535977200_CIT0001","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1128\/MR.59.1.94-123.1995","article-title":"Protein-protein interactions: methods for detection and analysis","volume":"59","author":"Phizicky","year":"1995","journal-title":"Microbiol Rev"},{"issue":"9","key":"2021033115535977200_CIT0002","first-page":"1027","article-title":"Protein\u2013protein interactions define specificity in signal transduction","volume":"14","author":"Pawson","year":"2000"},{"issue":"4","key":"2021033115535977200_CIT0003","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/j.molcel.2011.12.034","article-title":"Dynamic protein-protein interaction wiring of the human spliceosome","volume":"45","author":"Hegele","year":"2012","journal-title":"Mol Cell"},{"issue":"2","key":"2021033115535977200_CIT0004","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1074\/mcp.M100026-MCP200","article-title":"Describing biological protein interactions in terms of protein states and state transitions","volume":"1","author":"Duan","year":"2002","journal-title":"Mol Cell Proteomics"},{"issue":"1","key":"2021033115535977200_CIT0005","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.drudis.2015.09.011","article-title":"Stabilization of protein\u2013protein interaction complexes through small molecules","volume":"21","author":"Zarzycka","year":"2016","journal-title":"Drug Discov Today"},{"issue":"4","key":"2021033115535977200_CIT0006","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1002\/pmic.200390053","article-title":"Protein-protein interactions as a target for drugs in proteomics","volume":"3","author":"Archakov","year":"2003","journal-title":"Proteomics"},{"issue":"1","key":"2021033115535977200_CIT0007","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nrg2484","article-title":"RNA-Seq: a revolutionary tool for transcriptomics","volume":"10","author":"Wang","year":"2009","journal-title":"Nat Rev Genet"},{"issue":"3","key":"2021033115535977200_CIT0008","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/nchembio.779","article-title":"Using transcriptome sequencing to identify mechanisms of drug action and resistance","volume":"8","author":"Wacker","year":"2012","journal-title":"Nat Chem Biol"},{"key":"2021033115535977200_CIT0009","first-page":"49","article-title":"Microarray analysis in drug discovery and clinical applications","volume":"316","author":"Wang","year":"2006","journal-title":"Methods Mol Biol"},{"issue":"5485","key":"2021033115535977200_CIT0010","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1126\/science.289.5485.1760","article-title":"Printing proteins as microarrays for high-throughput function determination","volume":"289","author":"MacBeath","year":"2000","journal-title":"Science"},{"issue":"2","key":"2021033115535977200_CIT0011","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1002\/bdrc.21096","article-title":"Thalidomide-induced teratogenesis: history and mechanisms","volume":"105","author":"Vargesson","year":"2015","journal-title":"Birth Defects Res C"},{"issue":"8","key":"2021033115535977200_CIT0012","doi-asserted-by":"crossref","first-page":"3968","DOI":"10.1182\/blood-2007-10-117457","article-title":"Thalidomide for treatment of multiple myeloma: 10 years later","volume":"111","author":"Palumbo","year":"2008","journal-title":"Blood"},{"issue":"11","key":"2021033115535977200_CIT0013","first-page":"5767","article-title":"Therapeutic potential of thalidomide and its analogues in the treatment of cancer","volume":"35","author":"Sherbet","year":"2015","journal-title":"Anticancer Res"},{"issue":"5","key":"2021033115535977200_CIT0014","doi-asserted-by":"crossref","first-page":"466","DOI":"10.3748\/wjg.v18.i5.466","article-title":"Thalidomide-based multidisciplinary treatment for patients with advanced hepatocellular carcinoma: a retrospective analysis","volume":"18","author":"Chen","year":"2012","journal-title":"World J Gastroenterol"},{"issue":"3\u20134","key":"2021033115535977200_CIT0015","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1159\/000081333","article-title":"Hepatocellular carcinoma with intra-atrial tumor thrombi. A report of three cases responsive to thalidomide treatment and literature review","volume":"67","author":"Chang","year":"2004","journal-title":"Oncology"},{"issue":"18","key":"2021033115535977200_CIT0016","doi-asserted-by":"crossref","first-page":"3175","DOI":"10.1002\/pmic.201500108","article-title":"Quantitative proteomics using SILAC: principles, applications, and developments","volume":"15","author":"Chen","year":"2015","journal-title":"Proteomics"},{"issue":"9","key":"2021033115535977200_CIT0017","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1074\/mcp.M800113-MCP200","article-title":"Prevention of amino acid conversion in SILAC experiments with embryonic stem cells","volume":"7","author":"Bendall","year":"2008","journal-title":"Mol Cell Proteomics"},{"issue":"12","key":"2021033115535977200_CIT0018","doi-asserted-by":"crossref","first-page":"3720","DOI":"10.1016\/j.jprot.2012.04.035","article-title":"Effective correction of experimental errors in quantitative proteomics using stable isotope labeling by amino acids in cell culture (SILAC)","volume":"75","author":"Park","year":"2012","journal-title":"J Proteomics"},{"key":"2021033115535977200_CIT0019","unstructured":"User Guide: SILAC Protein Quantitation Kits issued by Thermo Fisher Scientific (Version: MAN0016245, Rev C.0, Pub. Part No. 2161996.8) . Available from: https:\/\/www.thermofisher.com\/"},{"issue":"3","key":"2021033115535977200_CIT0020","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1021\/pr8006107","article-title":"Evaluation of the variation in sample preparation for comparative proteomics using stable isotope labeling by amino acids in cell culture","volume":"8","author":"Zhang","year":"2009","journal-title":"J Proteome R"},{"key":"2021033115535977200_CIT0021","unstructured":"Cell Lysis and Immunoprecipitation Protocol with CHAPS buffer issued by Fivephoton BiochemicalsTM . Available from: https:\/\/fivephoton.com\/"},{"issue":"10","key":"2021033115535977200_CIT0022","doi-asserted-by":"crossref","first-page":"3623","DOI":"10.1021\/ac062292d","article-title":"Anion and cation mixed-bed ion exchange for enhanced multidimensional separations of peptides and phosphopeptides","volume":"79","author":"Motoyama","year":"2007","journal-title":"Anal Chem"},{"issue":"1\u20132","key":"2021033115535977200_CIT0023","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0167-4838(98)00121-6","article-title":"Acetonitrile-protein interactions: amino acid solubility and preferential solvation","volume":"1387","author":"Gekko","year":"1998","journal-title":"Biochim Biophys Acta"},{"key":"2021033115535977200_CIT0024","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.jpba.2016.08.019","article-title":"Impact of organic modifier and temperature on protein denaturation in hydrophobic interaction chromatography","volume":"131","author":"Bobaly","year":"2016","journal-title":"J Pharm Biomed Anal"},{"issue":"22","key":"2021033115535977200_CIT0025","doi-asserted-by":"crossref","first-page":"8484","DOI":"10.1021\/ac2017037","article-title":"A general protease digestion procedure for optimal protein sequence coverage and PTM analysis of recombinant glycoproteins: application to the characterization of hLOXL2 glycosylation","volume":"83","author":"Rebecchi","year":"2011","journal-title":"Anal Chem"},{"key":"2021033115535977200_CIT0026","unstructured":"Technical manual: Trypsin\/Lys-C Mix, Mass spec grade issued by Promega (Version: TM390 Revised 2\/14) . Available from: https:\/\/www.promega.com\/"},{"key":"2021033115535977200_CIT0027","unstructured":"GL-TipTM SDB Instruction Manual issued by GL Science . Available from: http:\/\/www.glsciencesinc.com\/"},{"key":"2021033115535977200_CIT0028","unstructured":"Proteome Discoverer User Guide Software Version 2.2 issued by Thermo Fisher Scientific . Available from: https:\/\/www.thermofisher.com\/"},{"issue":"5","key":"2021033115535977200_CIT0029","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1038\/ng.3537","article-title":"Transcriptomic and epigenomic characterization of the developing bat wing","volume":"48","author":"Eckalbar","year":"2016","journal-title":"Nature Genet"},{"issue":"11","key":"2021033115535977200_CIT0030","first-page":"5767","article-title":"Therapeutic potential of thalidomide and its analogues in the treatment of cancer","volume":"35","author":"Guglielmelli","year":"2015","journal-title":"Oncoscience"},{"issue":"4","key":"2021033115535977200_CIT0031","first-page":"382","article-title":"mTOR pathway activation in multiple myeloma cell lines and primary tumour cells: pomalidomide enhances cytoplasmic-nuclear shuttling of mTOR protein","volume":"2","author":"Sherbet","year":"2015","journal-title":"Anticancer Res"},{"issue":"8","key":"2021033115535977200_CIT0032","doi-asserted-by":"crossref","first-page":"e44228","DOI":"10.1371\/journal.pone.0044228","article-title":"Identification of thalidomide-specific transcriptomics and proteomics signatures during differentiation of human embryonic stem cells","volume":"7","author":"Meganathan","year":"2012","journal-title":"PLoS One"},{"issue":"2","key":"2021033115535977200_CIT0033","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.cellsig.2010.08.003","article-title":"The diverse functions of GAPDH: views from different subcellular compartments","volume":"23","author":"Tristan","year":"2011","journal-title":"Cell Signal"},{"issue":"17","key":"2021033115535977200_CIT0034","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1101\/gad.17268411","article-title":"Ending the message: poly(A) signals then and now","volume":"25","author":"Proudfoot","year":"2011","journal-title":"Genes Dev"},{"issue":"1","key":"2021033115535977200_CIT0035","doi-asserted-by":"crossref","first-page":"1716","DOI":"10.1038\/s41467-018-04112-z","article-title":"Widespread intronic polyadenylation diversifies immune cell transcriptomes","volume":"9","author":"Singh","year":"2018","journal-title":"Nat Commun"},{"issue":"12","key":"2021033115535977200_CIT0036","doi-asserted-by":"crossref","first-page":"1950","DOI":"10.1038\/sj.leu.2402295","article-title":"Adherence of multiple myeloma cells to bone marrow stromal cells upregulates vascular endothelial growth factor secretion: therapeutic applications","volume":"15","author":"Gupta","year":"2001","journal-title":"Leukemia"},{"issue":"13","key":"2021033115535977200_CIT0037","doi-asserted-by":"crossref","first-page":"4373","DOI":"10.1182\/blood-2006-07-038026","article-title":"Inhibition of adhesive interaction between multiple myeloma and bone marrow stromal cells by PPAR\u03b3 cross talk with NF-\u03baB and C\/EBP\u03b2","volume":"110","author":"Wang","year":"2007","journal-title":"Blood"},{"issue":"5","key":"2021033115535977200_CIT0038","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1038\/8466","article-title":"Free radical-mediated oxidative DNA damage in the mechanism of thalidomide teratogenicity","volume":"5","author":"Parman","year":"1999","journal-title":"Nat Med"},{"issue":"11","key":"2021033115535977200_CIT0039","doi-asserted-by":"crossref","first-page":"3503","DOI":"10.3390\/ijms19113503","article-title":"NRF2 is one of the players involved in bone marrow mediated drug resistance in multiple myeloma","volume":"19","author":"Yen","year":"2018","journal-title":"Int J Mol Sci"},{"issue":"4","key":"2021033115535977200_CIT0040","doi-asserted-by":"crossref","first-page":"2935","DOI":"10.3390\/biom5042935","article-title":"The RNA splicing response to DNA damage","volume":"5","author":"Shkreta","year":"2015","journal-title":"Biomolecules"},{"issue":"12","key":"2021033115535977200_CIT0041","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1016\/S0006-2952(99)00388-3","article-title":"Mechanism of action in thalidomide teratogenesis","volume":"59","author":"Stephens","year":"2000","journal-title":"Biochem Pharmacol"},{"issue":"20","key":"2021033115535977200_CIT0042","doi-asserted-by":"crossref","first-page":"7188","DOI":"10.1128\/MCB.00915-07","article-title":"NRF2 modulates aryl hydrocarbon receptor signaling: influence on adipogenesis","volume":"27","author":"Shin","year":"2007","journal-title":"Mol Cell Biol"},{"issue":"19","key":"2021033115535977200_CIT0043","doi-asserted-by":"crossref","first-page":"3608","DOI":"10.1016\/j.febslet.2007.03.046","article-title":"The aryl hydrocarbon receptor, more than a xenobiotic-interacting protein","volume":"581","author":"Baroukia","year":"2007","journal-title":"FEBS Lett"},{"issue":"6","key":"2021033115535977200_CIT0044","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1002\/iub.1040","article-title":"From protein interaction networks to novel therapeutic strategies","volume":"64","author":"Jaeger","year":"2012","journal-title":"IUBMB Life"},{"issue":"10","key":"2021033115535977200_CIT0045","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1016\/j.str.2010.08.007","article-title":"Transient protein-protein interactions: structural, functional, and network properties","volume":"18","author":"Perkins","year":"2010","journal-title":"Structure"}],"container-title":["Bioscience, Biotechnology, and Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/bbb\/article-pdf\/83\/11\/2034\/36834005\/bbb2034.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/bbb\/article-pdf\/83\/11\/2034\/36834005\/bbb2034.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T03:53:03Z","timestamp":1663905183000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bbb\/article\/83\/11\/2034\/5937969"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,2]]},"references-count":45,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2019,11,2]]},"published-print":{"date-parts":[[2019,11,2]]}},"URL":"https:\/\/doi.org\/10.1080\/09168451.2019.1637244","relation":{},"ISSN":["0916-8451","1347-6947"],"issn-type":[{"value":"0916-8451","type":"print"},{"value":"1347-6947","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,11,2]]},"published":{"date-parts":[[2019,11,2]]},"assertion":[{"value":"The publishing and review policy for this title is described in its Aims & Scope.","order":1,"name":"peerreview_statement","label":"Peer Review Statement"},{"value":"http:\/\/www.tandfonline.com\/action\/journalInformation?show=aimsScope&journalCode=tbbb20","URL":"http:\/\/www.tandfonline.com\/action\/journalInformation?show=aimsScope&journalCode=tbbb20","order":2,"name":"aims_and_scope_url","label":"Aim & Scope"},{"value":"2019-04-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-06-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}