Vaults: a ribonucleoprotein particle involved in drug resistance?

ABSTRACT Vaults are ribonucleoprotein particles found in the cytoplasm of eucaryotic cells. The 13 MDa particles are composed of multiple copies of three proteins: an _M_r 100 000 major

vault protein (MVP) and two minor vault proteins of _M_r 193 000 (vault poly-(ADP-ribose) polymerase) and _M_r 240 000 (telomerase-associated protein 1), as well as small untranslated RNA

molecules of approximately 100 bases. Although the existence of vaults was first reported in the mid-1980s no function has yet been attributed to this organelle. The notion that vaults might

play a role in drug resistance was suggested by the molecular identification of the lung resistance-related (LRP) protein as the human MVP. MVP/LRP was found to be overexpressed in many

chemoresistant cancer cell lines and primary tumor samples of different histogenetic origin. Several, but not all, clinico-pathological studies showed that MVP expression at diagnosis was an

independent adverse prognostic factor for response to chemotherapy. The hollow barrel-shaped structure of the vault complex and its subcellular localization indicate a function in

intracellular transport. It was therefore postulated that vaults contributed to drug resistance by transporting drugs away from their intracellular targets and/or the sequestration of drugs.

Here, we review the current knowledge on the vault complex and critically discuss the evidence that links vaults to drug resistance. Access through your institution Buy or subscribe This is

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EXOSOMAL CIRCRNAS IN TUMOUR IMMUNITY AND CANCER PROGRESSION Article Open access 09 June 2022 MOLECULAR FUNCTIONS AND THERAPEUTIC APPLICATIONS OF EXOSOMAL NONCODING RNAS IN CANCER Article

Open access 29 March 2022 TARGETING NON-CODING RNAS TO OVERCOME CANCER THERAPY RESISTANCE Article Open access 13 April 2022 ABBREVIATIONS * MVP: major vault protein * TEP1:

telomerase-associated protein * VPARP: vault poly-(ADP-ribose) polymerase * vRNA: vault RNA * LRP: lung resistance-related protein * P-gp: P-glycoprotein * MRP1: multidrug-resistance-related

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Biol. Chem._, 277, 40247–40252. Download references ACKNOWLEDGEMENTS We thank Erna Fränzel-Luiten, Martijn Schoester and George Scheffer for helpful discussions during the preparation of

this manuscript. This work was supported by a grant from the Dutch Cancer Society, # EUR 98-1754. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Hematology, Erasmus Medical

Center, PO Box 1738, Rotterdam, 3000 DR, The Netherlands Marieke H Mossink, Arend van Zon, Pieter Sonneveld & Erik AC Wiemer * Department of Pathology, Free University Medical Center,

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al._ Vaults: a ribonucleoprotein particle involved in drug resistance?. _Oncogene_ 22, 7458–7467 (2003). https://doi.org/10.1038/sj.onc.1206947 Download citation * Published: 23 October 2003

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Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * vault complex *

multidrug resistance * LRP * MVP