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Vaults: a ribonucleoprotein particle involved in drug resistance?

Oncogene volume 22, pages 7458–7467 (2003)Cite this article

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 Mr 100 000 major vault protein (MVP) and two minor vault proteins of Mr 193 000 (vault poly-(ADP-ribose) polymerase) and Mr 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.

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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 protein

BCRP:

breast cancer resistance protein

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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.

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  1. 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

  2. Department of Pathology, Free University Medical Center, Amsterdam, The Netherlands

    Rik J Scheper

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Mossink, M., van Zon, A., Scheper, R. et al. Vaults: a ribonucleoprotein particle involved in drug resistance?. Oncogene 22, 7458–7467 (2003). https://doi.org/10.1038/sj.onc.1206947

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