Vaults Are Up-regulated in Multidrug-resistant Cancer Cell Lines
Vaults are 13-MDa ribonucleoprotein particles composed largely of a 104-kDa protein, termed major vault protein or MVP, and a small vault RNA, vRNA. While MVP levels have been found to increase up to 15-fold in non-P-glycoprotein multidrug-resistant cell lines, the levels of vault particles have not...
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| Veröffentlicht in: | The Journal of biological chemistry 1998-04, Vol.273 (15), p.8971-8974 |
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| container_end_page | 8974 |
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| container_issue | 15 |
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| container_title | The Journal of biological chemistry |
| container_volume | 273 |
| creator | Kickhoefer, Valerie A. Rajavel, Kavitha S. Scheffer, George L. Dalton, William S. Scheper, Rik J. Rome, Leonard H. |
| description | Vaults are 13-MDa ribonucleoprotein particles composed largely of a 104-kDa protein, termed major vault protein or MVP, and a small vault RNA, vRNA. While MVP levels have been found to increase up to 15-fold in non-P-glycoprotein multidrug-resistant cell lines, the levels of vault particles have not been investigated. As both the function of vault particles and the mechanism of drug resistance in non-P-glycoprotein cells are unknown, we decided to determine whether vault synthesis was coupled to MDR. By cloning the human gene for vRNA and careful quantitation of the MVP and vRNA levels in MDR cells, we find that vRNA is in considerable excess to MVP. Sedimentation measurements of vault particles in multidrug resistance cells have indeed revealed up to a 15-fold increase in vault synthesis, coupled with a comparable shift of associated vRNA, demonstrating that vault formation is limited by expression of MVP or the minor vault proteins. The observation that vault synthesis is linked directly to multidrug resistance supports a direct role for vaults in drug resistance. |
| doi_str_mv | 10.1074/jbc.273.15.8971 |
| format | Article |
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While MVP levels have been found to increase up to 15-fold in non-P-glycoprotein multidrug-resistant cell lines, the levels of vault particles have not been investigated. As both the function of vault particles and the mechanism of drug resistance in non-P-glycoprotein cells are unknown, we decided to determine whether vault synthesis was coupled to MDR. By cloning the human gene for vRNA and careful quantitation of the MVP and vRNA levels in MDR cells, we find that vRNA is in considerable excess to MVP. Sedimentation measurements of vault particles in multidrug resistance cells have indeed revealed up to a 15-fold increase in vault synthesis, coupled with a comparable shift of associated vRNA, demonstrating that vault formation is limited by expression of MVP or the minor vault proteins. The observation that vault synthesis is linked directly to multidrug resistance supports a direct role for vaults in drug resistance.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.273.15.8971</identifier><identifier>PMID: 9535882</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Base Sequence ; Breast Neoplasms ; Carcinoma, Non-Small-Cell Lung ; Carcinoma, Small Cell ; Cloning, Organism ; Drug Resistance, Multiple ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms ; Molecular Sequence Data ; Multiple Myeloma ; Ribonucleoproteins - biosynthesis ; Ribonucleoproteins - genetics ; RNA - biosynthesis ; RNA - genetics ; Sequence Alignment ; Sequence Homology, Nucleic Acid ; Transcription, Genetic ; Tumor Cells, Cultured ; Vault Ribonucleoprotein Particles</subject><ispartof>The Journal of biological chemistry, 1998-04, Vol.273 (15), p.8971-8974</ispartof><rights>1998 © 1998 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c508t-346563ded40e4be4044c1d65800027b1e4a85fef5c50aaa750d0609129d59cdb3</citedby><cites>FETCH-LOGICAL-c508t-346563ded40e4be4044c1d65800027b1e4a85fef5c50aaa750d0609129d59cdb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9535882$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kickhoefer, Valerie A.</creatorcontrib><creatorcontrib>Rajavel, Kavitha S.</creatorcontrib><creatorcontrib>Scheffer, George L.</creatorcontrib><creatorcontrib>Dalton, William S.</creatorcontrib><creatorcontrib>Scheper, Rik J.</creatorcontrib><creatorcontrib>Rome, Leonard H.</creatorcontrib><title>Vaults Are Up-regulated in Multidrug-resistant Cancer Cell Lines</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>Vaults are 13-MDa ribonucleoprotein particles composed largely of a 104-kDa protein, termed major vault protein or MVP, and a small vault RNA, vRNA. While MVP levels have been found to increase up to 15-fold in non-P-glycoprotein multidrug-resistant cell lines, the levels of vault particles have not been investigated. As both the function of vault particles and the mechanism of drug resistance in non-P-glycoprotein cells are unknown, we decided to determine whether vault synthesis was coupled to MDR. By cloning the human gene for vRNA and careful quantitation of the MVP and vRNA levels in MDR cells, we find that vRNA is in considerable excess to MVP. Sedimentation measurements of vault particles in multidrug resistance cells have indeed revealed up to a 15-fold increase in vault synthesis, coupled with a comparable shift of associated vRNA, demonstrating that vault formation is limited by expression of MVP or the minor vault proteins. The observation that vault synthesis is linked directly to multidrug resistance supports a direct role for vaults in drug resistance.</description><subject>Base Sequence</subject><subject>Breast Neoplasms</subject><subject>Carcinoma, Non-Small-Cell Lung</subject><subject>Carcinoma, Small Cell</subject><subject>Cloning, Organism</subject><subject>Drug Resistance, Multiple</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Lung Neoplasms</subject><subject>Molecular Sequence Data</subject><subject>Multiple Myeloma</subject><subject>Ribonucleoproteins - biosynthesis</subject><subject>Ribonucleoproteins - genetics</subject><subject>RNA - biosynthesis</subject><subject>RNA - genetics</subject><subject>Sequence Alignment</subject><subject>Sequence Homology, Nucleic Acid</subject><subject>Transcription, Genetic</subject><subject>Tumor Cells, Cultured</subject><subject>Vault Ribonucleoprotein Particles</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkM1LwzAYh4MoOj_OnoSC4K1b3jZpk5tS_IKJFxVvIU3ebZGunUmr-N-bseFBEHMJ5Pe8b348hJwCHQMt2eStNuOszMfAx0KWsENGQEWe5hxed8mI0gxSmXFxQA5DeKPxMAn7ZF_ynAuRjcjlix6aPiRXHpPnVepxPjS6R5u4NnmIibN-mMfn4EKv2z6pdGvQJxU2TTJ1LYZjsjfTTcCT7X1Enm-un6q7dPp4e19dTVPDqejTnBW8yC1aRpHVyChjBmzBRayUlTUg04LPcMYjrrUuObW0oBIyabk0ts6PyMVm78p37wOGXi1dMLGGbrEbgiplKQGA_gtCET-XhYjgZAMa34XgcaZW3i21_1JA1VquinJVlKuAq7XcOHG2XT3US7Q__NZmzM83-cLNF5_Oo6pdZxa4_LVFbiiMuj4cehWMw6jVxgnTK9u5Pxt8A6cxkr4</recordid><startdate>19980410</startdate><enddate>19980410</enddate><creator>Kickhoefer, Valerie A.</creator><creator>Rajavel, Kavitha S.</creator><creator>Scheffer, George L.</creator><creator>Dalton, William S.</creator><creator>Scheper, Rik J.</creator><creator>Rome, Leonard H.</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>19980410</creationdate><title>Vaults Are Up-regulated in Multidrug-resistant Cancer Cell Lines</title><author>Kickhoefer, Valerie A. ; Rajavel, Kavitha S. ; Scheffer, George L. ; Dalton, William S. ; Scheper, Rik J. ; Rome, Leonard H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c508t-346563ded40e4be4044c1d65800027b1e4a85fef5c50aaa750d0609129d59cdb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Base Sequence</topic><topic>Breast Neoplasms</topic><topic>Carcinoma, Non-Small-Cell Lung</topic><topic>Carcinoma, Small Cell</topic><topic>Cloning, Organism</topic><topic>Drug Resistance, Multiple</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Lung Neoplasms</topic><topic>Molecular Sequence Data</topic><topic>Multiple Myeloma</topic><topic>Ribonucleoproteins - biosynthesis</topic><topic>Ribonucleoproteins - genetics</topic><topic>RNA - biosynthesis</topic><topic>RNA - genetics</topic><topic>Sequence Alignment</topic><topic>Sequence Homology, Nucleic Acid</topic><topic>Transcription, Genetic</topic><topic>Tumor Cells, Cultured</topic><topic>Vault Ribonucleoprotein Particles</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kickhoefer, Valerie A.</creatorcontrib><creatorcontrib>Rajavel, Kavitha S.</creatorcontrib><creatorcontrib>Scheffer, George L.</creatorcontrib><creatorcontrib>Dalton, William S.</creatorcontrib><creatorcontrib>Scheper, Rik J.</creatorcontrib><creatorcontrib>Rome, Leonard H.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kickhoefer, Valerie A.</au><au>Rajavel, Kavitha S.</au><au>Scheffer, George L.</au><au>Dalton, William S.</au><au>Scheper, Rik J.</au><au>Rome, Leonard H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Vaults Are Up-regulated in Multidrug-resistant Cancer Cell Lines</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>1998-04-10</date><risdate>1998</risdate><volume>273</volume><issue>15</issue><spage>8971</spage><epage>8974</epage><pages>8971-8974</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>Vaults are 13-MDa ribonucleoprotein particles composed largely of a 104-kDa protein, termed major vault protein or MVP, and a small vault RNA, vRNA. While MVP levels have been found to increase up to 15-fold in non-P-glycoprotein multidrug-resistant cell lines, the levels of vault particles have not been investigated. As both the function of vault particles and the mechanism of drug resistance in non-P-glycoprotein cells are unknown, we decided to determine whether vault synthesis was coupled to MDR. By cloning the human gene for vRNA and careful quantitation of the MVP and vRNA levels in MDR cells, we find that vRNA is in considerable excess to MVP. Sedimentation measurements of vault particles in multidrug resistance cells have indeed revealed up to a 15-fold increase in vault synthesis, coupled with a comparable shift of associated vRNA, demonstrating that vault formation is limited by expression of MVP or the minor vault proteins. 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| identifier | ISSN: 0021-9258 |
| ispartof | The Journal of biological chemistry, 1998-04, Vol.273 (15), p.8971-8974 |
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| language | eng |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Base Sequence Breast Neoplasms Carcinoma, Non-Small-Cell Lung Carcinoma, Small Cell Cloning, Organism Drug Resistance, Multiple Female Gene Expression Regulation, Neoplastic Humans Lung Neoplasms Molecular Sequence Data Multiple Myeloma Ribonucleoproteins - biosynthesis Ribonucleoproteins - genetics RNA - biosynthesis RNA - genetics Sequence Alignment Sequence Homology, Nucleic Acid Transcription, Genetic Tumor Cells, Cultured Vault Ribonucleoprotein Particles |
| title | Vaults Are Up-regulated in Multidrug-resistant Cancer Cell Lines |
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