Ontology type: schema:ScholarlyArticle Open Access: True
2011-04
AUTHORSP Karna, P C G Rida, V Pannu, K K Gupta, W B Dalton, H Joshi, V W Yang, J Zhou, R Aneja
ABSTRACTWe have previously shown that a non-toxic noscapinoid, EM011 binds tubulin without altering its monomer/polymer ratio. EM011 is more active than the parent molecule, noscapine, in inducing G2/M arrest, inhibiting cellular proliferation and tumor growth in various human xenograft models. However, the mechanisms of mitotic-block and subsequent cell death have remained elusive. Here, we show that EM011-induced attenuation of microtubule dynamics was associated with impaired association of microtubule plus-end tracking proteins, such as EB1 and CLIP-170. EM011 treatment then led to the formation of multipolar spindles containing 'real' centrioles indicating drug-induced centrosome amplification and persistent centrosome declustering. Centrosome amplification was accompanied by an upregulation of Aurora A and Plk4 protein levels, as well as a surge in the kinase activity of Aurora A, suggesting a deregulation of the centrosome duplication cycle. Cell-cycle phase-specific experiments showed that the 'cytotoxicity-window' of the drug encompasses the late S-G2 period. Drug-treatment, excluding S-phase, not only resulted in lower sub-G1 population but also attenuated centrosome amplification and spindle multipolarity, suggesting that drug-induced centrosome amplification is essential for maximal cell death. Subsequent to a robust mitotic arrest, EM011-treated cells displayed diverse cellular fates suggesting a high degree of intraline variation. Some 'apoptosis-evasive' cells underwent aberrant cytokinesis to generate rampant aneuploidy that perhaps contributed to drug-induced cell death. These data indicate that spindle multipolarity induction by means of centrosome amplification has an exciting chemotherapeutic potential that merits further investigation. More... »
PAGES632
http://scigraph.springernature.com/pub.10.1038/cdd.2010.133
DOIhttp://dx.doi.org/10.1038/cdd.2010.133
DIMENSIONShttps://app.dimensions.ai/details/publication/pub.1029500774
PUBMEDhttps://www.ncbi.nlm.nih.gov/pubmed/21052096
JSON-LD is the canonical representation for SciGraph data.
TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT
[
{
"@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json",
"about": [
{
"id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0601",
"inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/",
"name": "Biochemistry and Cell Biology",
"type": "DefinedTerm"
},
{
"id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/06",
"inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/",
"name": "Biological Sciences",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Apoptosis",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Aurora Kinases",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Cell Line, Tumor",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Centrosome",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Dioxoles",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "G1 Phase",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "G2 Phase",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Humans",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Isoquinolines",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Microtubule-Associated Proteins",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Microtubules",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Mitosis",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Neoplasm Proteins",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Protein-Serine-Threonine Kinases",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "S Phase",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Spindle Apparatus",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Tubulin Modulators",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Up-Regulation",
"type": "DefinedTerm"
}
],
"author": [
{
"affiliation": {
"alternateName": "Georgia State University",
"id": "https://www.grid.ac/institutes/grid.256304.6",
"name": [
"Department of Biology, Georgia State University, Atlanta, GA, USA"
],
"type": "Organization"
},
"familyName": "Karna",
"givenName": "P",
"id": "sg:person.01062177433.98",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01062177433.98"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Emory University",
"id": "https://www.grid.ac/institutes/grid.189967.8",
"name": [
"Department of Cell Biology, Emory University School of Medicine, Atlanta, GA, USA"
],
"type": "Organization"
},
"familyName": "Rida",
"givenName": "P C G",
"id": "sg:person.016623704504.45",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016623704504.45"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Georgia State University",
"id": "https://www.grid.ac/institutes/grid.256304.6",
"name": [
"Department of Biology, Georgia State University, Atlanta, GA, USA"
],
"type": "Organization"
},
"familyName": "Pannu",
"givenName": "V",
"id": "sg:person.01176426033.62",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01176426033.62"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "University of Notre Dame",
"id": "https://www.grid.ac/institutes/grid.131063.6",
"name": [
"Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, USA"
],
"type": "Organization"
},
"familyName": "Gupta",
"givenName": "K K",
"id": "sg:person.01113125367.51",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01113125367.51"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Emory University",
"id": "https://www.grid.ac/institutes/grid.189967.8",
"name": [
"Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA"
],
"type": "Organization"
},
"familyName": "Dalton",
"givenName": "W B",
"id": "sg:person.01005050072.89",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01005050072.89"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Emory University",
"id": "https://www.grid.ac/institutes/grid.189967.8",
"name": [
"Department of Cell Biology, Emory University School of Medicine, Atlanta, GA, USA"
],
"type": "Organization"
},
"familyName": "Joshi",
"givenName": "H",
"id": "sg:person.01171123402.11",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01171123402.11"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Emory University",
"id": "https://www.grid.ac/institutes/grid.189967.8",
"name": [
"Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA"
],
"type": "Organization"
},
"familyName": "Yang",
"givenName": "V W",
"id": "sg:person.0721076573.37",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0721076573.37"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Nankai University",
"id": "https://www.grid.ac/institutes/grid.216938.7",
"name": [
"Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, Tianjin, China"
],
"type": "Organization"
},
"familyName": "Zhou",
"givenName": "J",
"id": "sg:person.016271610257.07",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016271610257.07"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Georgia State University",
"id": "https://www.grid.ac/institutes/grid.256304.6",
"name": [
"Department of Biology, Georgia State University, Atlanta, GA, USA"
],
"type": "Organization"
},
"familyName": "Aneja",
"givenName": "R",
"id": "sg:person.01365356361.20",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01365356361.20"
],
"type": "Person"
}
],
"citation": [
{
"id": "https://doi.org/10.1182/blood-2005-12-5142",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1000286059"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1002/em.20533",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1000386807"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1002/em.20533",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1000386807"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nrc1714",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1001299857",
"https://doi.org/10.1038/nrc1714"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nrc1714",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1001299857",
"https://doi.org/10.1038/nrc1714"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1182/blood-2005-08-3516",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1001506031"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nrc924",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1007068023",
"https://doi.org/10.1038/nrc924"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nrc924",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1007068023",
"https://doi.org/10.1038/nrc924"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1158/1535-7163.mct-08-0156",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1007143533"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1124/mol.105.021899",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1007448764"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1083/jcb.200910142",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1008390624"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1002/jcb.22099",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1011842296"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/j.bcp.2006.05.004",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1012673538"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1124/mol.63.4.799",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1014462655"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1091/mbc.6.9.1215",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1014817102"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1091/mbc.e02-08-0510",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1016268553"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1002/ijc.24765",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1017134873"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1002/ijc.24765",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1017134873"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/j.canlet.2005.07.005",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1017201401"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1158/0008-5472.can-05-2962",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1018717882"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/s0955-0674(01)00290-3",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1020030867"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1073/pnas.90.20.9552",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1020300773"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/0305-7372(94)90027-2",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1023040730"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/s0962-8924(00)01872-9",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1025319775"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/j.ccr.2008.07.002",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1026742955"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1083/jcb.130.1.105",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1026871669"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1186/1476-4598-8-93",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1028313535",
"https://doi.org/10.1186/1476-4598-8-93"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/ncb1320",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1029819465",
"https://doi.org/10.1038/ncb1320"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/ncb1320",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1029819465",
"https://doi.org/10.1038/ncb1320"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1038/sj.emboj.7600916",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1030311799"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1038/sj.emboj.7600916",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1030311799"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/j.cell.2008.05.039",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1031209337"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1007/s002620000109",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1035502052",
"https://doi.org/10.1007/s002620000109"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/sj.onc.1210456",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1035649135",
"https://doi.org/10.1038/sj.onc.1210456"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/sj.onc.1210456",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1035649135",
"https://doi.org/10.1038/sj.onc.1210456"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1158/1535-7163.mct-06-0205",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1039841112"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1158/0008-5472.can-07-1874",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1041913597"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/j.ejca.2010.02.017",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1044028659"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1101/gad.1700908",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1044326402"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1093/emboj/21.4.483",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1047993728"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/0014-4827(73)90407-2",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1048847360"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1083/jcb.98.6.2222",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1049110929"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1073/pnas.95.4.1601",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1050085553"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1126/science.1104905",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1062451177"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.3233/clo-2008-0445",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1077725921"
],
"type": "CreativeWork"
},
{
"id": "https://app.dimensions.ai/details/publication/pub.1079523694",
"type": "CreativeWork"
},
{
"id": "https://app.dimensions.ai/details/publication/pub.1081707773",
"type": "CreativeWork"
}
],
"datePublished": "2011-04",
"datePublishedReg": "2011-04-01",
"description": "We have previously shown that a non-toxic noscapinoid, EM011 binds tubulin without altering its monomer/polymer ratio. EM011 is more active than the parent molecule, noscapine, in inducing G2/M arrest, inhibiting cellular proliferation and tumor growth in various human xenograft models. However, the mechanisms of mitotic-block and subsequent cell death have remained elusive. Here, we show that EM011-induced attenuation of microtubule dynamics was associated with impaired association of microtubule plus-end tracking proteins, such as EB1 and CLIP-170. EM011 treatment then led to the formation of multipolar spindles containing 'real' centrioles indicating drug-induced centrosome amplification and persistent centrosome declustering. Centrosome amplification was accompanied by an upregulation of Aurora A and Plk4 protein levels, as well as a surge in the kinase activity of Aurora A, suggesting a deregulation of the centrosome duplication cycle. Cell-cycle phase-specific experiments showed that the 'cytotoxicity-window' of the drug encompasses the late S-G2 period. Drug-treatment, excluding S-phase, not only resulted in lower sub-G1 population but also attenuated centrosome amplification and spindle multipolarity, suggesting that drug-induced centrosome amplification is essential for maximal cell death. Subsequent to a robust mitotic arrest, EM011-treated cells displayed diverse cellular fates suggesting a high degree of intraline variation. Some 'apoptosis-evasive' cells underwent aberrant cytokinesis to generate rampant aneuploidy that perhaps contributed to drug-induced cell death. These data indicate that spindle multipolarity induction by means of centrosome amplification has an exciting chemotherapeutic potential that merits further investigation.",
"genre": "research_article",
"id": "sg:pub.10.1038/cdd.2010.133",
"inLanguage": [
"en"
],
"isAccessibleForFree": true,
"isFundedItemOf": [
{
"id": "sg:grant.2441509",
"type": "MonetaryGrant"
},
{
"id": "sg:grant.2683860",
"type": "MonetaryGrant"
}
],
"isPartOf": [
{
"id": "sg:journal.1112551",
"issn": [
"1350-9047",
"1476-5403"
],
"name": "Cell Death & Differentiation",
"type": "Periodical"
},
{
"issueNumber": "4",
"type": "PublicationIssue"
},
{
"type": "PublicationVolume",
"volumeNumber": "18"
}
],
"name": "A novel microtubule-modulating noscapinoid triggers apoptosis by inducing spindle multipolarity via centrosome amplification and declustering",
"pagination": "632",
"productId": [
{
"name": "readcube_id",
"type": "PropertyValue",
"value": [
"8c89a4a92b40d5ec231b855d17d493e89ef0edbbce17658a948ed3c799fb7399"
]
},
{
"name": "pubmed_id",
"type": "PropertyValue",
"value": [
"21052096"
]
},
{
"name": "nlm_unique_id",
"type": "PropertyValue",
"value": [
"9437445"
]
},
{
"name": "doi",
"type": "PropertyValue",
"value": [
"10.1038/cdd.2010.133"
]
},
{
"name": "dimensions_id",
"type": "PropertyValue",
"value": [
"pub.1029500774"
]
}
],
"sameAs": [
"https://doi.org/10.1038/cdd.2010.133",
"https://app.dimensions.ai/details/publication/pub.1029500774"
],
"sdDataset": "articles",
"sdDatePublished": "2019-04-10T21:26",
"sdLicense": "https://scigraph.springernature.com/explorer/license/",
"sdPublisher": {
"name": "Springer Nature - SN SciGraph project",
"type": "Organization"
},
"sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000001_0000000264/records_8687_00000438.jsonl",
"type": "ScholarlyArticle",
"url": "https://www.nature.com/articles/cdd2010133"
}
]Download the RDF metadata as: json-ld nt turtle xml License info
JSON-LD is a popular format for linked data which is fully compatible with JSON.
curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/cdd.2010.133'
N-Triples is a line-based linked data format ideal for batch operations.
curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/cdd.2010.133'
Turtle is a human-readable linked data format.
curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/cdd.2010.133'
RDF/XML is a standard XML format for linked data.
curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/cdd.2010.133'
This table displays all metadata directly associated to this object as RDF triples.
335 TRIPLES
21 PREDICATES
87 URIs
39 LITERALS
27 BLANK NODES