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Vaults Are Up-regulated in Multidrug-resistant Cancer Cell Lines
Open accessAbstract
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.
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Overexpression of a Transporter Gene in a Multidrug-Resistant Human Lung Cancer Cell Line
Cole, S. P. C., Bhardwaj, G., Gerlach, J. H., Mackie, J. E., Grant, C. E., Almquist, K. C., Stewart, A. J., Kurz, E. U., Duncan, A. M. V., & Deeley, R. G. (1992) · Science · doi:10.1126/science.1360704 · Cited by 3,037
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Mechanisms of Multidrug Resistance in Cancer
Gillet, J.-P., & Gottesman, M. M. (2010) · Methods in Molecular Biology · doi:10.1007/978-1-60761-416-6_4 · Cited by 685
Protein Repeats: Structures, Functions, and Evolution
Andrade, M. A., Perez-Iratxeta, C., & Ponting, C. P. (2001) · Journal of Structural Biology · doi:10.1006/jsbi.2001.4392 · Cited by 615
The challenge of drug resistance in cancer treatment: a current overview
Nikolaou, M., Pavlopoulou, A., Georgakilas, A. G., & Kyrodimos, E. (2018) · Clinical & Experimental Metastasis · doi:10.1007/s10585-018-9903-0 · Cited by 600
Hassa, P. (2008) · Frontiers in Bioscience · doi:10.2741/2909 · Cited by 584
Patterns of Known and Novel Small RNAs in Human Cervical Cancer
Lui, W.-O., Pourmand, N., Patterson, B. K., & Fire, A. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-0561 · Cited by 432
Metadata
- Authors
- Kickhoefer, V. A., Rajavel, K. S., Scheffer, G. L., Dalton, W. S., Scheper, R. J., & Rome, L. H.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1998-04
- Volume
- 273
- Issue
- 15
- Pages
- 8971-8974
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2031832448
- Cited by
- 248
- References
- 1
- FWCI
- 5.77
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Kickhoefer, V. A., Rajavel, K. S., Scheffer, G. L., Dalton, W. S., Scheper, R. J., & Rome, L. H. (1998). Vaults Are Up-regulated in Multidrug-resistant Cancer Cell Lines. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.273.15.8971
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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