Sjögren syndrome/scleroderma autoantigen 1 is a direct Tankyrase binding partner in cancer cells.


Journal

Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179

Informations de publication

Date de publication:
13 03 2020
Historique:
received: 30 10 2019
accepted: 21 02 2020
entrez: 15 3 2020
pubmed: 15 3 2020
medline: 10 2 2021
Statut: epublish

Résumé

Sjögren syndrome/scleroderma autoantigen 1 (SSSCA1) was first described as an auto-antigen over-expressed in Sjögren's syndrome and in scleroderma patients. SSSCA1 has been linked to mitosis and centromere association and as a potential marker candidate in diverse solid cancers. Here we characterize SSSCA1 for the first time, to our knowledge, at the molecular, structural and subcellular level. We have determined the crystal structure of a zinc finger fold, a zinc ribbon domain type 2 (ZNRD2), at 2.3 Å resolution. We show that the C-terminal domain serves a dual function as it both behaves as the interaction site to Tankyrase 1 (TNKS1) and as a nuclear export signal. We identify TNKS1 as a direct binding partner of SSSCA1, map the binding site to TNKS1 ankyrin repeat cluster 2 (ARC2) and thus define a new binding sequence. We experimentally verify and map a new nuclear export signal sequence in SSSCA1.

Identifiants

pubmed: 32170109
doi: 10.1038/s42003-020-0851-2
pii: 10.1038/s42003-020-0851-2
pmc: PMC7070046
doi:

Substances chimiques

Autoantigens 0
Nuclear Export Signals 0
Ribonucleoproteins 0
SS-A antigen 0
Tankyrases EC 2.4.2.30
TNKS protein, human EC 2.4.4.30

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

123

Références

Muro, Y., Yamada, T., Himeno, M. & Sugimoto, K. cDNA cloning of a novel autoantigen targeted by a minor subset of anti-centromere antibodies. Clin. Exp. Immunol. 111, 372–376 (1998).
pubmed: 9486406 pmcid: 1904897 doi: 10.1046/j.1365-2249.1998.00517.x
Sakuma-Takagi, M. et al. Novel related cDNAs (C184L, C184M, and C184S) from developing mouse brain encoding two apparently unrelated proteins. Biochem. Biophys. Res. Commun. 263, 737–742 (1999).
pubmed: 10512749 doi: 10.1006/bbrc.1999.1462
Uhlen, M. et al. Towards a knowledge-based Human Protein Atlas. Nat. Biotechnol. 28, 1248–1250 (2010).
pubmed: 21139605 doi: 10.1038/nbt1210-1248
Wang, M., Herrmann, C. J., Simonovic, M., Szklarczyk, D. & von Mering, C. Version 4.0 of PaxDb: protein abundance data, integrated across model organisms, tissues, and cell-lines. Proteomics 15, 3163–3168 (2015).
pubmed: 25656970 pmcid: 6680238 doi: 10.1002/pmic.201400441
Li, X. et al. Proteomic Analysis of the Human Tankyrase Protein Interaction Network Reveals Its Role in Pexophagy. Cell Rep. 20, 737–749 (2017).
pubmed: 28723574 doi: 10.1016/j.celrep.2017.06.077
Huang, S. M. et al. Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature 461, 614–620 (2009).
pubmed: 19759537 doi: 10.1038/nature08356
Voronkov, A. et al. Structural basis and SAR for G007-LK, a lead stage 1,2,4-triazole based specific tankyrase 1/2 inhibitor. J. Med. Chem. 56, 3012–3023 (2013).
pubmed: 23473363 doi: 10.1021/jm4000566
Zhang, Y. et al. RNF146 is a poly(ADP-ribose)-directed E3 ligase that regulates axin degradation and Wnt signalling. Nat. Cell Biol. 13, 623–629 (2011).
pubmed: 21478859 doi: 10.1038/ncb2222
Giles, R. H., van Es, J. H. & Clevers, H. Caught up in a Wnt storm: Wnt signaling in cancer. Biochim. et. Biophys. Acta 1653, 1–24 (2003).
Sillars-Hardebol, A. H. et al. Identification of key genes for carcinogenic pathways associated with colorectal adenoma-to-carcinoma progression. Tumour Biol. 31, 89–96 (2010).
pubmed: 20358421 pmcid: 2848338 doi: 10.1007/s13277-009-0012-1
Sillars-Hardebol, A. H., Carvalho, B., van Engeland, M., Fijneman, R. J. & Meijer, G. A. The adenoma hunt in colorectal cancer screening: defining the target. J. Pathol. 226, 1–6 (2012).
pubmed: 21984228 doi: 10.1002/path.3012
Vendrell, J. A. et al. A candidate molecular signature associated with tamoxifen failure in primary breast cancer. Breast Cancer Res. 10, R88 (2008).
pubmed: 18928543 pmcid: 2614524 doi: 10.1186/bcr2158
Baxter, J. S. et al. Capture Hi-C identifies putative target genes at 33 breast cancer risk loci. Nat. Commun. 9, 1028 (2018).
pubmed: 29531215 pmcid: 5847529 doi: 10.1038/s41467-018-03411-9
Ferreira, M. A. et al. Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer. Nat. Commun. 10, 1741 (2019).
pubmed: 30988301 pmcid: 6465407 doi: 10.1038/s41467-018-08053-5
Xu, C. et al. Integrative analysis of DNA copy number and gene expression in metastatic oral squamous cell carcinoma identifies genes associated with poor survival. Mol. Cancer 9, 143 (2010).
pubmed: 20537188 pmcid: 2893102 doi: 10.1186/1476-4598-9-143
Stigliani, S. et al. High genomic instability predicts survival in metastatic high-risk neuroblastoma. Neoplasia 14, 823–832 (2012).
pubmed: 23019414 pmcid: 3459278 doi: 10.1593/neo.121114
Xue, A. et al. Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes. Nat. Commun. 9, 2941 (2018).
pubmed: 30054458 pmcid: 30054458 doi: 10.1038/s41467-018-04951-w
Huttlin, E. L. et al. The BioPlex network: a systematic exploration of the human interactome. Cell 162, 425–440 (2015).
pubmed: 26186194 pmcid: 4617211 doi: 10.1016/j.cell.2015.06.043
Al-Hakim, A. K., Bashkurov, M., Gingras, A. C., Durocher, D. & Pelletier, L. Interaction proteomics identify NEURL4 and the HECT E3 ligase HERC2 as novel modulators of centrosome architecture. Mol. Cell Proteom. 11, M111 014233 (2012).
doi: 10.1074/mcp.M111.014233
Kim, T. Y. et al. Substrate trapping proteomics reveals targets of the betaTrCP2/FBXW11 ubiquitin ligase. Mol. Cell Biol. 35, 167–181 (2015).
pubmed: 25332235 doi: 10.1128/MCB.00857-14
Kim, W. et al. Systematic and quantitative assessment of the ubiquitin-modified proteome. Mol. Cell 44, 325–340 (2011).
pubmed: 21906983 pmcid: 3200427 doi: 10.1016/j.molcel.2011.08.025
Danielsen, J. M. et al. Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level. Mol. Cell Proteom. 10, M110 003590 (2011).
doi: 10.1074/mcp.M110.003590
Udeshi, N. D. et al. Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition. Mol. Cell Proteom. 11, 148–159 (2012).
doi: 10.1074/mcp.M111.016857
Mertins, P. et al. Integrated proteomic analysis of post-translational modifications by serial enrichment. Nat. Methods 10, 634–637 (2013).
pubmed: 23749302 pmcid: 3943163 doi: 10.1038/nmeth.2518
Finn, R. D. et al. The Pfam protein families database: towards a more sustainable future. Nucleic Acids Res. 44, D279–D285 (2016).
pubmed: 26673716 doi: 10.1093/nar/gkv1344
Gregorieff, A. & Clevers, H. Wnt signaling in the intestinal epithelium: from endoderm to cancer. Genes Dev. 19, 877–890 (2005).
pubmed: 15833914 doi: 10.1101/gad.1295405
Anastas, J. N. & Moon, R. T. WNT signalling pathways as therapeutic targets in cancer. Nat. Rev. Cancer 13, 11–26 (2013).
pubmed: 23258168 doi: 10.1038/nrc3419
Gingras, A. C., Gstaiger, M., Raught, B. & Aebersold, R. Analysis of protein complexes using mass spectrometry. Nat. Rev. Mol. Cell Biol. 8, 645–654 (2007).
pubmed: 17593931 doi: 10.1038/nrm2208
Huang da, W., Sherman, B. T. & Lempicki, R. A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc. 4, 44–57 (2009).
doi: 10.1038/nprot.2008.211
Ashburner, M. et al. Gene Ontology: tool for the unification of biology. Nat. Genet. 25, 25–29 (2000).
pubmed: 3037419 pmcid: 3037419 doi: 10.1038/75556
Jensen, L. J. et al. STRING 8-a global view on proteins and their functional interactions in 630 organisms. Nucleic Acids Res. 37, D412–D416 (2009).
pubmed: 18940858 doi: 10.1093/nar/gkn760
Morrone, S., Cheng, Z., Moon, R. T., Cong, F. & Xu, W. Crystal structure of a Tankyrase-Axin complex and its implications for Axin turnover and Tankyrase substrate recruitment. Proc. Natl Acad. Sci. USA 109, 1500–1505 (2012).
pubmed: 22307604 doi: 10.1073/pnas.1116618109
DaRosa, P. A. et al. Allosteric activation of the RNF146 ubiquitin ligase by a poly(ADP-ribosyl)ation signal. Nature 517, 223–226 (2015).
pubmed: 25327252 doi: 10.1038/nature13826
Pollock, K., Ranes, M., Collins, I. & Guettler, S. Identifying and validating Tankyrase binders and substrates: a candidate approach. Methods Mol. Biol. 1608, 445–473 (2017).
pubmed: 28695526 pmcid: 6082341 doi: 10.1007/978-1-4939-6993-7_28
Krissinel, E. & Henrick, K. Inference of macromolecular assemblies from crystalline state. J. Mol. Biol. 372, 774–797 (2007).
doi: 10.1016/j.jmb.2007.05.022
Holm, L. & Rosenstrom, P. Dali server: conservation mapping in 3D. Nucleic Acids Res. 38, W545–W549 (2010).
pubmed: 2896194 pmcid: 2896194 doi: 10.1093/nar/gkq366
Krissinel, E. & Henrick, K. Secondary-structure matching (SSM), a new tool for fast protein structure alignment in three dimensions. Acta Crystallogr. D. Biol. Crystallogr. 60, 2256–2268 (2004).
pubmed: 15572779 doi: 10.1107/S0907444904026460
Aragon, E. et al. A Smad action turnover switch operated by WW domain readers of a phosphoserine code. Genes Dev. 25, 1275–1288 (2011).
pubmed: 21685363 pmcid: 3127429 doi: 10.1101/gad.2060811
Meiyappan, M., Birrane, G. & Ladias, J. A. A. Structural basis for polyproline recognition by the FE65 WW domain. J. Mol. Biol. 372, 970–980 (2007).
pubmed: 17686488 pmcid: 2693091 doi: 10.1016/j.jmb.2007.06.064
Qi, S., O’Hayre, M., Gutkind, J. S. & Hurley, J. H. Structural and biochemical basis for ubiquitin ligase recruitment by arrestin-related domain-containing protein-3 (ARRDC3). J. Biol. Chem. 289, 4743–4752 (2014).
pubmed: 24379409 doi: 10.1074/jbc.M113.527473
Engel, C., Sainsbury, S., Cheung, A. C., Kostrewa, D. & Cramer, P. RNA polymerase I structure and transcription regulation. Nature 502, 650–655 (2013).
pubmed: 24153182 doi: 10.1038/nature12712
la Cour, T. et al. Analysis and prediction of leucine-rich nuclear export signals. Protein Eng. Des. Sel. 17, 527–536 (2004).
pubmed: 15314210 doi: 10.1093/protein/gzh062
Wen, W., Meinkoth, J. L., Tsien, R. Y. & Taylor, S. S. Identification of a signal for rapid export of proteins from the nucleus. Cell 82, 463–473 (1995).
pubmed: 7634336 doi: 10.1016/0092-8674(95)90435-2
Hwang, I. S., Woo, S. U., Park, J. W., Lee, S. K. & Yim, H. Two nuclear export signals of Cdc6 are differentially associated with CDK-mediated phosphorylation residues for cytoplasmic translocation. Biochim. et. Biophys. Acta 1843, 223–233 (2014).
doi: 10.1016/j.bbamcr.2013.10.024
Taylor, T. D. et al. Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature 440, 497–500 (2006).
pubmed: 16554811 doi: 10.1038/nature04632
Koreth, J., Bakkenist, C. J. & McGee, J. O. Chromosomes, 11Q and cancer: a review. J. Pathol. 187, 28–38 (1999).
pubmed: 10341704 doi: 10.1002/(SICI)1096-9896(199901)187:1<28::AID-PATH166>3.0.CO;2-R
Lammie, G. A. & Peters, G. Chromosome 11q13 abnormalities in human cancer. Cancer Cells 3, 413–420 (1991).
pubmed: 1760243
Srivatsan, E. S. et al. Localization of deletion to a 300 Kb interval of chromosome 11q13 in cervical cancer. Oncogene 21, 5631–5642 (2002).
pubmed: 12165862 doi: 10.1038/sj.onc.1205698
Rosa-Rosa, J. M. et al. A 7 Mb region within 11q13 may contain a high penetrance gene for breast cancer. Breast Cancer Res. Treat. 118, 151–159 (2009).
pubmed: 19205878 doi: 10.1007/s10549-009-0317-1
Chung, C. C. et al. Fine mapping of a region of chromosome 11q13 reveals multiple independent loci associated with risk of prostate cancer. Hum. Mol. Genet 20, 2869–2878 (2011).
pubmed: 21531787 pmcid: 3118760 doi: 10.1093/hmg/ddr189
International Chicken Genome Sequencing, C. Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution. Nature 432, 695–716 (2004).
doi: 10.1038/nature03154
Adams, M. D. et al. The genome sequence of Drosophila melanogaster. Science 287, 2185–2195 (2000).
doi: 10.1126/science.287.5461.2185
Smith, S. & de Lange, T. Tankyrase promotes telomere elongation in human cells. Curr. Biol. 10, 1299–1302 (2000).
pubmed: 11069113 doi: 10.1016/S0960-9822(00)00752-1
Chang, P., Coughlin, M. & Mitchison, T. J. Tankyrase-1 polymerization of poly(ADP-ribose) is required for spindle structure and function. Nat. Cell Biol. 7, 1133–1139 (2005).
pubmed: 16244666 doi: 10.1038/ncb1322
Callow, M. G. et al. Ubiquitin ligase RNF146 regulates tankyrase and Axin to promote Wnt signaling. PloS One 6, e22595 (2011).
pubmed: 21799911 pmcid: 3143158 doi: 10.1371/journal.pone.0022595
Wang, Z. et al. Recognition of the iso-ADP-ribose moiety in poly(ADP-ribose) by WWE domains suggests a general mechanism for poly(ADP-ribosyl)ation-dependent ubiquitination. Genes Dev. 26, 235–240 (2012).
pubmed: 22267412 pmcid: 3278890 doi: 10.1101/gad.182618.111
Chi, N. W. & Lodish, H. F. Tankyrase is a golgi-associated mitogen-activated protein kinase substrate that interacts with IRAP in GLUT4 vesicles. J. Biol. Chem. 275, 38437–38444 (2000).
pubmed: 10988299 doi: 10.1074/jbc.M007635200
Lau, T. et al. A novel tankyrase small-molecule inhibitor suppresses APC mutation-driven colorectal tumor growth. Cancer Res. 73, 3132–3144 (2013).
pubmed: 23539443 doi: 10.1158/0008-5472.CAN-12-4562
Scarborough, H. A. et al. AZ1366: an inhibitor of Tankyrase and the canonical Wnt pathway that limits the persistence of non-small cell lung cancer cells following EGFR inhibition. Clin. Cancer Res. 23, 1531–1541 (2017).
pubmed: 27663586 doi: 10.1158/1078-0432.CCR-16-1179
Grigoryan, T., Wend, P., Klaus, A. & Birchmeier, W. Deciphering the function of canonical Wnt signals in development and disease: conditional loss- and gain-of-function mutations of beta-catenin in mice. Genes Dev. 22, 2308–2341 (2008).
pubmed: 18765787 pmcid: 2749675 doi: 10.1101/gad.1686208
Guettler, S. et al. Structural basis and sequence rules for substrate recognition by Tankyrase explain the basis for cherubism disease. Cell 147, 1340–1354 (2011).
pubmed: 22153077 doi: 10.1016/j.cell.2011.10.046
Bork, P. & Sudol, M. The WW domain: a signalling site in dystrophin? Trends Biochem. Sci. 19, 531–533 (1994).
pubmed: 7846762 doi: 10.1016/0968-0004(94)90053-1
Uversky, V. N., Oldfield, C. J. & Dunker, A. K. Intrinsically disordered proteins in human diseases: introducing the D2 concept. Annu. Rev. Biophys. 37, 215–246 (2008).
pubmed: 18573080 doi: 10.1146/annurev.biophys.37.032807.125924
Liu, J. et al. Intrinsic disorder in transcription factors. Biochemistry 45, 6873–6888 (2006).
pubmed: 16734424 pmcid: 2538555 doi: 10.1021/bi0602718
Wright, P. E. & Dyson, H. J. Linking folding and binding. Curr. Opin. Struct. Biol. 19, 31–38 (2009).
pubmed: 19157855 pmcid: 2675572 doi: 10.1016/j.sbi.2008.12.003
Hilser, V. J. & Thompson, E. B. Intrinsic disorder as a mechanism to optimize allosteric coupling in proteins. Proc. Natl Acad. Sci. USA 104, 8311–8315 (2007).
pubmed: 17494761 doi: 10.1073/pnas.0700329104
Kosugi, S., Hasebe, M., Tomita, M. & Yanagawa, H. Nuclear export signal consensus sequences defined using a localization-based yeast selection system. Traffic 9, 2053–2062 (2008).
pubmed: 18817528 doi: 10.1111/j.1600-0854.2008.00825.x
Lee, Y., Pei, J., Baumhardt, J. M., Chook, Y. M. & Grishin, N. V. Structural prerequisites for CRM1-dependent nuclear export signaling peptides: accessibility, adapting conformation, and the stability at the binding site. Sci. Rep. 9, 6627 (2019).
pubmed: 31036839 pmcid: 6488578 doi: 10.1038/s41598-019-43004-0
Kirli, K. et al. A deep proteomics perspective on CRM1-mediated nuclear export and nucleocytoplasmic partitioning. Elife. 4, https://doi.org/10.7554/eLife.11466 (2015).
Xue, B., Dunbrack, R. L., Williams, R. W., Dunker, A. K. & Uversky, V. N. PONDR-FIT: a meta-predictor of intrinsically disordered amino acids. Biochim. et. Biophys. Acta 1804, 996–1010 (2010).
doi: 10.1016/j.bbapap.2010.01.011
Kawate, T. & Gouaux, E. Fluorescence-detection size-exclusion chromatography for precrystallization screening of integral membrane proteins. Structure 14, 673–681 (2006).
pubmed: 16615909 doi: 10.1016/j.str.2006.01.013
Ishihama, Y. et al. Exponentially modified protein abundance index (emPAI) for estimation of absolute protein amount in proteomics by the number of sequenced peptides per protein. Mol. Cell Proteom. 4, 1265–1272 (2005).
doi: 10.1074/mcp.M500061-MCP200
Eisemann, T. et al. Tankyrase-1 ankyrin repeats form an adaptable binding platform for targets of ADP-ribose modification. Structure 24, 1679–1692 (2016).
pubmed: 27594684 doi: 10.1016/j.str.2016.07.014
McCoy, A. J. et al. Phaser crystallographic software. J. Appl. Crystallogr. 40, 658–674 (2007).
pubmed: 19461840 pmcid: 19461840 doi: 10.1107/S0021889807021206
Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D. Biol. Crystallogr. 66, 486–501 (2010).
pubmed: 20383002 pmcid: 2852313 doi: 10.1107/S0907444910007493
Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D. Biol. Crystallogr. 66, 213–221 (2010).
pubmed: 2815670 pmcid: 2815670 doi: 10.1107/S0907444909052925
Murshudov, G. N., Vagin, A. A. & Dodson, E. J. Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr. D. Biol. Crystallogr. 53, 240–255 (1997).
doi: 10.1107/S0907444996012255
Chen, V. B. et al. MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr. D. Biol. Crystallogr. 66, 12–21 (2010).
doi: 10.1107/S0907444909042073

Auteurs

Harmonie Perdreau-Dahl (H)

Membrane Transport Group, Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo, P.O. Box 1137 Blindern, 0318, Oslo, Norway.
Institute for Experimental Medical Research (IEMR), Oslo University Hospital, Ullevål PB 4956 Nydalen, NO-0424, Oslo, Norway.

Cinzia Progida (C)

Centre for Immune Regulation, Department of Molecular Biosciences, University of Oslo, Blindernveien 31, 0371, Oslo, Norway.

Stefan J Barfeld (SJ)

Prostate Cancer Group, Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo, P.O. Box 1137 Blindern, 0318, Oslo, Norway.

Hanne Guldsten (H)

Membrane Transport Group, Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo, P.O. Box 1137 Blindern, 0318, Oslo, Norway.

Bernd Thiede (B)

Department of Biosciences, University of Oslo, P.O. Box 1137 Blindern, 0316, Oslo, Norway.

Magnus Arntzen (M)

Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, P.O. Box 5003, N-1432, Ås, Norway.

Oddmund Bakke (O)

Centre for Immune Regulation, Department of Molecular Biosciences, University of Oslo, Blindernveien 31, 0371, Oslo, Norway.

Ian G Mills (IG)

Prostate Cancer Group, Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo, P.O. Box 1137 Blindern, 0318, Oslo, Norway.
Patrick G Johnston Centre for Cancer Research, Queens University Belfast, Belfast, UK.
Nuffield Department of Surgical Sciences, Faculty of Medical Science, University of Oxford, John Radcliffe Hospital, Oxford, UK.

Stefan Krauss (S)

Department of Immunology and Transfusion Medicine, Oslo University Hospital, and Hybrid Technology Hub-Centre of Excellence, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.

J Preben Morth (JP)

Membrane Transport Group, Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo, P.O. Box 1137 Blindern, 0318, Oslo, Norway. premo@dtu.dk.
Institute for Experimental Medical Research (IEMR), Oslo University Hospital, Ullevål PB 4956 Nydalen, NO-0424, Oslo, Norway. premo@dtu.dk.
Enzyme and Protein Chemistry, Section for Protein Chemistry and Enzyme Technology, Department of Biotechnology and Biomedicine, Technical University of Denmark, Søltofts Plads, 2800, Kgs. Lyngby, Denmark. premo@dtu.dk.

Articles similaires

Genome, Chloroplast Phylogeny Genetic Markers Base Composition High-Throughput Nucleotide Sequencing

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C

Classifications MeSH