Abstract
Vaults are evolutionary highly conserved ribonucleoproteins particles with a hollow barrel-like structure. The main component of vaults represents the 110 kDa major vault protein (MVP), whereas two minor vaults proteins comprise the 193 kDa vault poly(ADP-ribose) polymerase (vPARP) and the 240 kDa telomerase-associated protein-1 (TEP-1). Additionally, at least one small and untranslated RNA is found as a constitutive component. MVP seems to play an important role in the development of multidrug resistance. This particle has also been implicated in the regulation of several cellular processes including transport mechanisms, signal transmission and immune responses. Vaults are considered a prognostic marker for different cancer types. The level of MVP expression predicts the clinical outcome after chemotherapy in different tumour types. Recently, new roles have been assigned to MVP and vaults including the association with the insulin-like growth factor-1, hypoxia-inducible factor-1alpha, and the two major DNA double-strand break repair machineries: non-homologous endjoining and homologous recombination. Furthermore, MVP has been proposed as a useful prognostic factor associated with radiotherapy resistance. Here, we review these novel actions of vaults and discuss a putative role of MVP and vaults in the response to radiotherapy.
Highlights
Vaults are evolutionary highly conserved ribonucleoproteins particles with a hollow barrel-like structure
Major vault protein: an overview of structure and composition Vaults are ribonucleoprotein particles with a hollow barrel-like structure [1] and a mass of 13 MD. It is composed of three proteins: major vault protein (MVP) (104 kD), the vault poly(adenosine diphosphate-ribose) polymerase known as VPARP (193 kD), and telomerase-associated protein-1 TEP1 (240 kD), and small untranslated RNA of 141 bases
VPARP presumably ribosylates substrates and TEP1 is important for stabilization of vRNA
Summary
Vaults are ubiquitous ribonucleoprotein complexes involved in a diversity of cellular processes, including multidrug resistance, transport mechanisms, signal transmission and immune response. New roles have been assigned to MVP in the field of radiotherapy, where vaults have been proposed as a useful prognostic marker associated with radiotherapy resistance. The molecular mechanisms behind this relevant role are unknown, a possible association with relevant key players in non-homologous endjoining repair and homologous recombination could exist. Additional translational and clinical studies are required to test this hypothesis. List of abbreviations HIF-1: hypoxia-inducible factor-1; HR: homologous recombination; MDR: multidrug resistance; MRP: multidrug resistance protein; MVP: major vaults protein; NHEJ: non-homologous end joining; RT: radiotherapy; TEP-1: telomerase-associated protein-1; VPARP: vault poly(adenosine diphosphateribose) polymerase
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