Targeting HSP90 and monoclonal protein trafficking modulates the unfolded protein response, chaperone regulation and apoptosis in myeloma cells View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-12

AUTHORS

E J Born, S V Hartman, S A Holstein

ABSTRACT

Multiple myeloma is characterized by the production of substantial quantities of monoclonal protein. We have previously demonstrated that select inhibitors of the isoprenoid biosynthetic pathway (IBP) induce apoptosis of myeloma cells via inhibition of Rab geranylgeranylation, leading to disruption of monoclonal protein trafficking and induction of the unfolded protein response (UPR) pathway. Heat-shock protein 90 (HSP90) inhibitors disrupt protein folding and are currently under clinical investigation in myeloma. The effects of combining IBP and HSP90 inhibitors on cell death, monoclonal protein trafficking, the UPR and chaperone regulation were investigated in monoclonal protein-producing cells. An enhanced induction of cell death was observed following treatment with IBP and HSP90 inhibitors, which occurred through both ER stress and non-ER stress pathways. The HSP90 inhibitor 17-AAG abrogated the effects of the IBP inhibitors on intracellular monoclonal protein levels and localization as well as induction of the UPR in myeloma cells. Disparate effects on chaperone expression were observed in myeloma vs amyloid light chain cells. Here we demonstrate that the novel strategy of targeting MP trafficking in concert with HSP90 enhances myeloma cell death via a complex modulation of ER stress, UPR, and cell death pathways. More... »

PAGES

e167

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/bcj.2013.64

DOI

http://dx.doi.org/10.1038/bcj.2013.64

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1043323970

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24317089


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

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"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "University of Iowa", 
          "id": "https://www.grid.ac/institutes/grid.214572.7", 
          "name": [
            "Department of Internal Medicine, University of Iowa, Iowa City, IA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Born", 
        "givenName": "E J", 
        "id": "sg:person.01166344074.46", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01166344074.46"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Integrated DNA Technologies (United States)", 
          "id": "https://www.grid.ac/institutes/grid.420360.3", 
          "name": [
            "Integrated DNA Technologies, Coralville, IA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Hartman", 
        "givenName": "S V", 
        "id": "sg:person.01221517020.23", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01221517020.23"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Iowa", 
          "id": "https://www.grid.ac/institutes/grid.214572.7", 
          "name": [
            "Department of Internal Medicine, University of Iowa, Iowa City, IA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Holstein", 
        "givenName": "S A", 
        "id": "sg:person.0746626060.37", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0746626060.37"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "sg:pub.10.1007/s00280-007-0546-0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1002248964", 
          "https://doi.org/10.1007/s00280-007-0546-0"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s00280-007-0546-0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1002248964", 
          "https://doi.org/10.1007/s00280-007-0546-0"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1006/mthe.2002.0639", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1002309154"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/1535-7163.mct-08-0186", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1002945078"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1182/blood-2005-08-3531", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003212965"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1182/blood-2008-03-143040", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1004168949"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.m502685200", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005107786"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.m502685200", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005107786"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.cdd.4401378", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005764407", 
          "https://doi.org/10.1038/sj.cdd.4401378"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.cdd.4401378", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005764407", 
          "https://doi.org/10.1038/sj.cdd.4401378"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/leu.2013.150", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1007231370", 
          "https://doi.org/10.1038/leu.2013.150"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1083/jcb.200310015", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010364982"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/j.1742-4658.2007.05735.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1019779278"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1167/iovs.06-0943", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1020177501"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/47513", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1020577355", 
          "https://doi.org/10.1038/47513"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/47513", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1020577355", 
          "https://doi.org/10.1038/47513"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1207108", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1022002237", 
          "https://doi.org/10.1038/sj.onc.1207108"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1207108", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1022002237", 
          "https://doi.org/10.1038/sj.onc.1207108"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1182/blood-2006-11-053728", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1023022480"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/leu.2008.111", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1023236154", 
          "https://doi.org/10.1038/leu.2008.111"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/0065-2571(84)90007-4", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026371633"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/0065-2571(84)90007-4", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026371633"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.leukres.2010.08.008", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1030063168"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/mcb.20.18.6755-6767.2000", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1030967835"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/bcj.2012.13", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033218961", 
          "https://doi.org/10.1038/bcj.2012.13"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1182/blood-2005-03-1158", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1034954160"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.m702672200", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1041019416"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/16729", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1041694590", 
          "https://doi.org/10.1038/16729"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/16729", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1041694590", 
          "https://doi.org/10.1038/16729"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s12192-012-0351-5", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1041878480", 
          "https://doi.org/10.1007/s12192-012-0351-5"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/j.1365-2141.2011.08664.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043558810"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0022-2836(02)00234-6", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1044040852"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.m204973200", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045011974"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/hep.23209", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045584648"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/hep.23209", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045584648"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0145-2126(00)00162-4", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1046048736"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/370373a0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1046473215", 
          "https://doi.org/10.1038/370373a0"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.bmc.2006.02.010", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1047094760"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ni1149", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1047239620", 
          "https://doi.org/10.1038/ni1149"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ni1149", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1047239620", 
          "https://doi.org/10.1038/ni1149"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ni1149", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1047239620", 
          "https://doi.org/10.1038/ni1149"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/j.1471-4159.2006.03782.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1047421351"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/j.1471-4159.2006.03782.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1047421351"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1101/gad.6.3.439", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1049557807"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.semcdb.2007.09.003", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1049621337"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/leu.2010.168", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1050491547", 
          "https://doi.org/10.1038/leu.2010.168"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1080/10428190500472123", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1058362266"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/01.asn.0000129826.28932.fd", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1060319620"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/01.asn.0000129826.28932.fd", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1060319620"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/01.asn.0000129826.28932.fd", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1060319620"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.2174/138945011798829339", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1069181976"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.m106473200", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1074888125"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1078817218", 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2013-12", 
    "datePublishedReg": "2013-12-01", 
    "description": "Multiple myeloma is characterized by the production of substantial quantities of monoclonal protein. We have previously demonstrated that select inhibitors of the isoprenoid biosynthetic pathway (IBP) induce apoptosis of myeloma cells via inhibition of Rab geranylgeranylation, leading to disruption of monoclonal protein trafficking and induction of the unfolded protein response (UPR) pathway. Heat-shock protein 90 (HSP90) inhibitors disrupt protein folding and are currently under clinical investigation in myeloma. The effects of combining IBP and HSP90 inhibitors on cell death, monoclonal protein trafficking, the UPR and chaperone regulation were investigated in monoclonal protein-producing cells. An enhanced induction of cell death was observed following treatment with IBP and HSP90 inhibitors, which occurred through both ER stress and non-ER stress pathways. The HSP90 inhibitor 17-AAG abrogated the effects of the IBP inhibitors on intracellular monoclonal protein levels and localization as well as induction of the UPR in myeloma cells. Disparate effects on chaperone expression were observed in myeloma vs amyloid light chain cells. Here we demonstrate that the novel strategy of targeting MP trafficking in concert with HSP90 enhances myeloma cell death via a complex modulation of ER stress, UPR, and cell death pathways. ", 
    "genre": "research_article", 
    "id": "sg:pub.10.1038/bcj.2013.64", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": true, 
    "isFundedItemOf": [
      {
        "id": "sg:grant.2482148", 
        "type": "MonetaryGrant"
      }
    ], 
    "isPartOf": [
      {
        "id": "sg:journal.1045682", 
        "issn": [
          "2044-5385"
        ], 
        "name": "Blood Cancer Journal", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "12", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "3"
      }
    ], 
    "name": "Targeting HSP90 and monoclonal protein trafficking modulates the unfolded protein response, chaperone regulation and apoptosis in myeloma cells", 
    "pagination": "e167", 
    "productId": [
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/bcj.2013.64"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1043323970"
        ]
      }, 
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "ce5e80d21fae0bfe8e514befb77e71f9508477b6c3504b881c45c9cb3c0230e6"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "101568469"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "24317089"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/bcj.2013.64", 
      "https://app.dimensions.ai/details/publication/pub.1043323970"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-16T06:21", 
    "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/v90/0000000377_0000000377/records_106807_00000001.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://www.nature.com/articles/bcj201364"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

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/bcj.2013.64'

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/bcj.2013.64'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/bcj.2013.64'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/bcj.2013.64'


 

This table displays all metadata directly associated to this object as RDF triples.

218 TRIPLES      21 PREDICATES      69 URIs      21 LITERALS      9 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/bcj.2013.64 schema:about anzsrc-for:06
2 anzsrc-for:0601
3 schema:author Na29933d6b1e640beb121332e88815e14
4 schema:citation sg:pub.10.1007/s00280-007-0546-0
5 sg:pub.10.1007/s12192-012-0351-5
6 sg:pub.10.1038/16729
7 sg:pub.10.1038/370373a0
8 sg:pub.10.1038/47513
9 sg:pub.10.1038/bcj.2012.13
10 sg:pub.10.1038/leu.2008.111
11 sg:pub.10.1038/leu.2010.168
12 sg:pub.10.1038/leu.2013.150
13 sg:pub.10.1038/ni1149
14 sg:pub.10.1038/sj.cdd.4401378
15 sg:pub.10.1038/sj.onc.1207108
16 https://app.dimensions.ai/details/publication/pub.1078817218
17 https://doi.org/10.1002/hep.23209
18 https://doi.org/10.1006/mthe.2002.0639
19 https://doi.org/10.1016/0065-2571(84)90007-4
20 https://doi.org/10.1016/j.bmc.2006.02.010
21 https://doi.org/10.1016/j.leukres.2010.08.008
22 https://doi.org/10.1016/j.semcdb.2007.09.003
23 https://doi.org/10.1016/s0022-2836(02)00234-6
24 https://doi.org/10.1016/s0145-2126(00)00162-4
25 https://doi.org/10.1074/jbc.m106473200
26 https://doi.org/10.1074/jbc.m204973200
27 https://doi.org/10.1074/jbc.m502685200
28 https://doi.org/10.1074/jbc.m702672200
29 https://doi.org/10.1080/10428190500472123
30 https://doi.org/10.1083/jcb.200310015
31 https://doi.org/10.1097/01.asn.0000129826.28932.fd
32 https://doi.org/10.1101/gad.6.3.439
33 https://doi.org/10.1111/j.1365-2141.2011.08664.x
34 https://doi.org/10.1111/j.1471-4159.2006.03782.x
35 https://doi.org/10.1111/j.1742-4658.2007.05735.x
36 https://doi.org/10.1128/mcb.20.18.6755-6767.2000
37 https://doi.org/10.1158/1535-7163.mct-08-0186
38 https://doi.org/10.1167/iovs.06-0943
39 https://doi.org/10.1182/blood-2005-03-1158
40 https://doi.org/10.1182/blood-2005-08-3531
41 https://doi.org/10.1182/blood-2006-11-053728
42 https://doi.org/10.1182/blood-2008-03-143040
43 https://doi.org/10.2174/138945011798829339
44 schema:datePublished 2013-12
45 schema:datePublishedReg 2013-12-01
46 schema:description Multiple myeloma is characterized by the production of substantial quantities of monoclonal protein. We have previously demonstrated that select inhibitors of the isoprenoid biosynthetic pathway (IBP) induce apoptosis of myeloma cells via inhibition of Rab geranylgeranylation, leading to disruption of monoclonal protein trafficking and induction of the unfolded protein response (UPR) pathway. Heat-shock protein 90 (HSP90) inhibitors disrupt protein folding and are currently under clinical investigation in myeloma. The effects of combining IBP and HSP90 inhibitors on cell death, monoclonal protein trafficking, the UPR and chaperone regulation were investigated in monoclonal protein-producing cells. An enhanced induction of cell death was observed following treatment with IBP and HSP90 inhibitors, which occurred through both ER stress and non-ER stress pathways. The HSP90 inhibitor 17-AAG abrogated the effects of the IBP inhibitors on intracellular monoclonal protein levels and localization as well as induction of the UPR in myeloma cells. Disparate effects on chaperone expression were observed in myeloma vs amyloid light chain cells. Here we demonstrate that the novel strategy of targeting MP trafficking in concert with HSP90 enhances myeloma cell death via a complex modulation of ER stress, UPR, and cell death pathways.
47 schema:genre research_article
48 schema:inLanguage en
49 schema:isAccessibleForFree true
50 schema:isPartOf N35dc369d143b426092823936b845deb2
51 N591d46e662764a1ab841256ae72f2f39
52 sg:journal.1045682
53 schema:name Targeting HSP90 and monoclonal protein trafficking modulates the unfolded protein response, chaperone regulation and apoptosis in myeloma cells
54 schema:pagination e167
55 schema:productId N21f48b439aab4ba08b832538f805b06d
56 N462e5dd9169f4cf885e6549f48465d85
57 N8eae0b44317643f78f82db9521e3810c
58 Nc2480b6da9f7499285398193357f086d
59 Nf6d3706528334e189e0cccb5b32fa1b1
60 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043323970
61 https://doi.org/10.1038/bcj.2013.64
62 schema:sdDatePublished 2019-04-16T06:21
63 schema:sdLicense https://scigraph.springernature.com/explorer/license/
64 schema:sdPublisher Ne2eb38d3441b473bbc104e77ee84ce21
65 schema:url https://www.nature.com/articles/bcj201364
66 sgo:license sg:explorer/license/
67 sgo:sdDataset articles
68 rdf:type schema:ScholarlyArticle
69 N19431947d39744639c6ee931503ed772 rdf:first sg:person.01221517020.23
70 rdf:rest N8605dca553774bba9715222a89ffe96f
71 N21f48b439aab4ba08b832538f805b06d schema:name dimensions_id
72 schema:value pub.1043323970
73 rdf:type schema:PropertyValue
74 N35dc369d143b426092823936b845deb2 schema:volumeNumber 3
75 rdf:type schema:PublicationVolume
76 N462e5dd9169f4cf885e6549f48465d85 schema:name readcube_id
77 schema:value ce5e80d21fae0bfe8e514befb77e71f9508477b6c3504b881c45c9cb3c0230e6
78 rdf:type schema:PropertyValue
79 N591d46e662764a1ab841256ae72f2f39 schema:issueNumber 12
80 rdf:type schema:PublicationIssue
81 N8605dca553774bba9715222a89ffe96f rdf:first sg:person.0746626060.37
82 rdf:rest rdf:nil
83 N8eae0b44317643f78f82db9521e3810c schema:name pubmed_id
84 schema:value 24317089
85 rdf:type schema:PropertyValue
86 Na29933d6b1e640beb121332e88815e14 rdf:first sg:person.01166344074.46
87 rdf:rest N19431947d39744639c6ee931503ed772
88 Nc2480b6da9f7499285398193357f086d schema:name nlm_unique_id
89 schema:value 101568469
90 rdf:type schema:PropertyValue
91 Ne2eb38d3441b473bbc104e77ee84ce21 schema:name Springer Nature - SN SciGraph project
92 rdf:type schema:Organization
93 Nf6d3706528334e189e0cccb5b32fa1b1 schema:name doi
94 schema:value 10.1038/bcj.2013.64
95 rdf:type schema:PropertyValue
96 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
97 schema:name Biological Sciences
98 rdf:type schema:DefinedTerm
99 anzsrc-for:0601 schema:inDefinedTermSet anzsrc-for:
100 schema:name Biochemistry and Cell Biology
101 rdf:type schema:DefinedTerm
102 sg:grant.2482148 http://pending.schema.org/fundedItem sg:pub.10.1038/bcj.2013.64
103 rdf:type schema:MonetaryGrant
104 sg:journal.1045682 schema:issn 2044-5385
105 schema:name Blood Cancer Journal
106 rdf:type schema:Periodical
107 sg:person.01166344074.46 schema:affiliation https://www.grid.ac/institutes/grid.214572.7
108 schema:familyName Born
109 schema:givenName E J
110 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01166344074.46
111 rdf:type schema:Person
112 sg:person.01221517020.23 schema:affiliation https://www.grid.ac/institutes/grid.420360.3
113 schema:familyName Hartman
114 schema:givenName S V
115 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01221517020.23
116 rdf:type schema:Person
117 sg:person.0746626060.37 schema:affiliation https://www.grid.ac/institutes/grid.214572.7
118 schema:familyName Holstein
119 schema:givenName S A
120 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0746626060.37
121 rdf:type schema:Person
122 sg:pub.10.1007/s00280-007-0546-0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002248964
123 https://doi.org/10.1007/s00280-007-0546-0
124 rdf:type schema:CreativeWork
125 sg:pub.10.1007/s12192-012-0351-5 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041878480
126 https://doi.org/10.1007/s12192-012-0351-5
127 rdf:type schema:CreativeWork
128 sg:pub.10.1038/16729 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041694590
129 https://doi.org/10.1038/16729
130 rdf:type schema:CreativeWork
131 sg:pub.10.1038/370373a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046473215
132 https://doi.org/10.1038/370373a0
133 rdf:type schema:CreativeWork
134 sg:pub.10.1038/47513 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020577355
135 https://doi.org/10.1038/47513
136 rdf:type schema:CreativeWork
137 sg:pub.10.1038/bcj.2012.13 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033218961
138 https://doi.org/10.1038/bcj.2012.13
139 rdf:type schema:CreativeWork
140 sg:pub.10.1038/leu.2008.111 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023236154
141 https://doi.org/10.1038/leu.2008.111
142 rdf:type schema:CreativeWork
143 sg:pub.10.1038/leu.2010.168 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050491547
144 https://doi.org/10.1038/leu.2010.168
145 rdf:type schema:CreativeWork
146 sg:pub.10.1038/leu.2013.150 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007231370
147 https://doi.org/10.1038/leu.2013.150
148 rdf:type schema:CreativeWork
149 sg:pub.10.1038/ni1149 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047239620
150 https://doi.org/10.1038/ni1149
151 rdf:type schema:CreativeWork
152 sg:pub.10.1038/sj.cdd.4401378 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005764407
153 https://doi.org/10.1038/sj.cdd.4401378
154 rdf:type schema:CreativeWork
155 sg:pub.10.1038/sj.onc.1207108 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022002237
156 https://doi.org/10.1038/sj.onc.1207108
157 rdf:type schema:CreativeWork
158 https://app.dimensions.ai/details/publication/pub.1078817218 schema:CreativeWork
159 https://doi.org/10.1002/hep.23209 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045584648
160 rdf:type schema:CreativeWork
161 https://doi.org/10.1006/mthe.2002.0639 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002309154
162 rdf:type schema:CreativeWork
163 https://doi.org/10.1016/0065-2571(84)90007-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026371633
164 rdf:type schema:CreativeWork
165 https://doi.org/10.1016/j.bmc.2006.02.010 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047094760
166 rdf:type schema:CreativeWork
167 https://doi.org/10.1016/j.leukres.2010.08.008 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030063168
168 rdf:type schema:CreativeWork
169 https://doi.org/10.1016/j.semcdb.2007.09.003 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049621337
170 rdf:type schema:CreativeWork
171 https://doi.org/10.1016/s0022-2836(02)00234-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044040852
172 rdf:type schema:CreativeWork
173 https://doi.org/10.1016/s0145-2126(00)00162-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046048736
174 rdf:type schema:CreativeWork
175 https://doi.org/10.1074/jbc.m106473200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1074888125
176 rdf:type schema:CreativeWork
177 https://doi.org/10.1074/jbc.m204973200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045011974
178 rdf:type schema:CreativeWork
179 https://doi.org/10.1074/jbc.m502685200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005107786
180 rdf:type schema:CreativeWork
181 https://doi.org/10.1074/jbc.m702672200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041019416
182 rdf:type schema:CreativeWork
183 https://doi.org/10.1080/10428190500472123 schema:sameAs https://app.dimensions.ai/details/publication/pub.1058362266
184 rdf:type schema:CreativeWork
185 https://doi.org/10.1083/jcb.200310015 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010364982
186 rdf:type schema:CreativeWork
187 https://doi.org/10.1097/01.asn.0000129826.28932.fd schema:sameAs https://app.dimensions.ai/details/publication/pub.1060319620
188 rdf:type schema:CreativeWork
189 https://doi.org/10.1101/gad.6.3.439 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049557807
190 rdf:type schema:CreativeWork
191 https://doi.org/10.1111/j.1365-2141.2011.08664.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1043558810
192 rdf:type schema:CreativeWork
193 https://doi.org/10.1111/j.1471-4159.2006.03782.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1047421351
194 rdf:type schema:CreativeWork
195 https://doi.org/10.1111/j.1742-4658.2007.05735.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1019779278
196 rdf:type schema:CreativeWork
197 https://doi.org/10.1128/mcb.20.18.6755-6767.2000 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030967835
198 rdf:type schema:CreativeWork
199 https://doi.org/10.1158/1535-7163.mct-08-0186 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002945078
200 rdf:type schema:CreativeWork
201 https://doi.org/10.1167/iovs.06-0943 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020177501
202 rdf:type schema:CreativeWork
203 https://doi.org/10.1182/blood-2005-03-1158 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034954160
204 rdf:type schema:CreativeWork
205 https://doi.org/10.1182/blood-2005-08-3531 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003212965
206 rdf:type schema:CreativeWork
207 https://doi.org/10.1182/blood-2006-11-053728 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023022480
208 rdf:type schema:CreativeWork
209 https://doi.org/10.1182/blood-2008-03-143040 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004168949
210 rdf:type schema:CreativeWork
211 https://doi.org/10.2174/138945011798829339 schema:sameAs https://app.dimensions.ai/details/publication/pub.1069181976
212 rdf:type schema:CreativeWork
213 https://www.grid.ac/institutes/grid.214572.7 schema:alternateName University of Iowa
214 schema:name Department of Internal Medicine, University of Iowa, Iowa City, IA, USA
215 rdf:type schema:Organization
216 https://www.grid.ac/institutes/grid.420360.3 schema:alternateName Integrated DNA Technologies (United States)
217 schema:name Integrated DNA Technologies, Coralville, IA, USA
218 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...