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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.
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.
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, Amsterdam, The Netherlands
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