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- Title
Vaults: a ribonucleoprotein particle involved in drug resistance?
- Authors
Mossink, Marieke H; van Zon, Arend; Scheper, Rik J; Sonneveld, Pieter; Wiemer, Erik AC
- 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.Oncogene (2003) 22, 7458-7467. doi:10.1038/sj.onc.1206947
- Subjects
NUCLEOPROTEINS; EUKARYOTIC cells; MULTIDRUG resistance; RNA; PROTEINS
- Publication
Oncogene, 2003, Vol 22, Issue 47, p7458
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1206947