Vaults: a ribonucleoprotein particle involved in drug resistance?
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.
Department of Hematology, Erasmus Medical Center, PO Box 1738, 3000 DR Rotterdam, The Netherlands.
Marieke H
MH
Mossink
Arend
A
van Zon
Rik J
RJ
Scheper
Pieter
P
Sonneveld
Erik A C
EA
Wiemer
D000818:Animals; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D020394:Vault Ribonucleoprotein Particles / Q000737:chemistry / Q000378:metabolism*; D000099187:Major Vault Protein
D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein