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"Vaults"
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Vault Particles in Cancer Progression, Multidrug Resistance, and Drug Delivery: Current Insights and Future Applications
Vault particles (VPs) are highly conserved large ribonucleoprotein complexes found exclusively in eukaryotes. They play critical roles in various cellular processes, but their involvement in cancer progression and multidrug resistance (MDR) is the most extensively studied. VPs are composed of the major vault protein (MVP), vault RNAs (vtRNAs), vault poly (ADP-ribose) polymerase, and telomerase-associated protein-1. These components are involved in the regulation of signaling pathways that affect tumor survival, proliferation, and metastasis. MVP has been associated with aggressive tumor phenotypes, while vtRNAs modulate cell proliferation, apoptosis, and autophagy. VPs also contribute to MDR by sequestering chemotherapeutic agents, altering their accumulation in the nucleus, and regulating lysosomal dynamics. Furthermore, small vault RNA-derived fragments participate in gene silencing and intercellular communication, reinforcing the role of precursors of vtRNAs in cancer development. Beyond their biological roles, VPs present a promising platform for drug delivery, due to their unique ability to encapsulate a wide range of biomolecules and therapeutic agents, followed by controlled release. This review compiles data from PubMed and Scopus, with a literature search conducted up until December 2024, highlighting current knowledge regarding VPs and their crucial involvement in cancer-related mechanisms and their applications in overcoming cancer drug resistance.
Journal Article
Innovative vaulting in the architecture of the Roman Empire : 1st to 4th centuries CE
\"This book studies six vaulting techniques employed in architecture outside of Rome and asks why they were invented where they were and how they were disseminated. Most of the techniques involve terracotta elements in various forms, such as regular flat bricks, hollow voussoirs, vaulting tubes, and armchair voussoirs. Each one is traced geographically via GIS mapping, the results of which are analysed in relation to chronology, geography, and historical context. The most common building type in which the techniques appear is the bath, demonstrating its importance as a catalyst for technological innovation. This book also explores trade networks, the pottery industry, and military movements in relation to building construction, revealing how architectural innovation was influenced by wide ranging cultural factors, many of which stemmed from local influences rather than imperial intervention\"-- Provided by publisher.
Book
Structural insights into the roles of PARP4 and NAD+ binding in the human vault cage
Vault is a massive ribonucleoprotein complex found across Eukaryota. The major vault protein (MVP) oligomerizes into an ovular cage, which contains several minor vault components (MVCs) and is thought to transport transiently bound “cargo” molecules. Vertebrate vaults house a poly (ADP-ribose) polymerase (known as PARP4 in humans), which is the only MVC with known enzymatic activity. Despite being discovered decades ago, the molecular basis for PARP4’s interaction with MVP remains unclear. In this study, we determined the structure of the human vault cage in complex with PARP4 and its enzymatic substrate NAD
+
. The structures reveal atomic-level details of the protein-binding interface, as well as unexpected binding sites for NAD
+
and related nucleotides within the interior of the vault cage. In addition, proteomics data show that human vaults purified from wild-type and PARP4-depleted cells interact with distinct subsets of proteins. Our results thereby support a model in which PARP4’s specific incorporation into the vault cage helps to regulate vault’s selection of cargo and its subcellular localization. Further, PARP4’s proximity to MVP’s NAD
+
-binding sites could support its enzymatic function within the vault.
Vaults are massive, cytoplasmic, cage-like ribonucleoprotein assemblies. Here, authors describe cryo-EM structures of human vault encapsulating PARP4 & nucleotide ligands, as well as proteomic data showing that depleting PARP4 alters the vault interactome.
Journal Article
Vaults and the major vault protein: Novel roles in signal pathway regulation and immunity
The unique and evolutionary highly conserved major vault protein (MVP) is the main component of ubiquitous, large cellular ribonucleoparticles termed vaults. The 100 kDa MVP represents more than 70% of the vault mass which contains two additional proteins, the vault poly (ADP-ribose) polymerase (vPARP) and the telomerase-associated protein 1 (TEP1), as well as several short untranslated RNAs (vRNA). Vaults are almost ubiquitously expressed and, besides chemotherapy resistance, have been implicated in the regulation of several cellular processes including transport mechanisms, signal transmissions and immune responses. Despite a growing amount of data from diverse species and systems, the definition of precise vault functions is still highly complex and challenging. Here we review the current knowledge on MVP and vaults with focus on regulatory functions in intracellular signal transduction and immune defence.
Journal Article
In Vitro Refolding of Vault-like Protein Nanocapsules with a Novel Scaffolding Mechanism
We attempted the in vitro scaffold-coordinated refolding of denatured major vault protein monomers into assembled vault-like nanoparticles. DNA or hyaluronic acid-binding tags were added to the MVP monomers, allowing MVP to align rotationally and translationally along these linear molecules. This was proposed to mimic the polyribosome assembly in vivo. Tagged MVP variants were expressed in E. coli and purified under denaturing conditions. Dynamic light scattering showed the formation of nanoparticles with a hydrodynamic radius of ~26 nm, consistent with the formation of vault-like nanoparticles. This was confirmed by transmission electron microscopy, FRET analysis, and cargo loading of CFP-INT fusion. CFP- and YFP-tagged MVP showed FRET only in the presence of MVP with a DNA-binding tag. This is the first successful instance of bioengineering of homogenous and heterogeneous vault-like nanoparticles, and at a potentially much larger scale than current protocols.
Journal Article
The vault associates with membranes in situ
The eukaryotic vault particle is a giant ribonucleoprotein complex that assembles into an iconic barrel-like cage. Its cellular function has remained elusive despite extensive characterization. Using cryo-electron tomography of
Dictyostelium discoideum
cells, we define the distribution, structural states, and interaction landscape of vault particles in situ. Surprisingly, we detect a subpopulation of vault particles associated with the endoplasmic reticulum (ER) and nuclear envelope membranes. This association occurs at a defined barrel height of the vault particle. Membrane-associated particles appear to localize to patches of reduced membrane bilayer thickness and altered curvature. We further find that a fraction of vaults encloses 80S ribosomes in highly ordered orientations. These structural findings are further corroborated by proximity labeling experiments, which identify ER-resident proteins and numerous ribosomal components as vault particle interactors. The membrane-bound and ribosome-encapsulating vault populations that we uncover will direct future studies towards revealing vault function.
Vault particles are giant ribonucleoprotein complexes with elusive cellular roles. Here, authors use cryo-electron tomography and proximity labeling to show that vaults associate with ER and nuclear envelope membranes and encapsulate 80S ribosomes in situ.
Journal Article
Numerical insights on the structural assessment of historical masonry stellar vaults: the case of Santa Maria del Monte in Cagliari
The aim of this paper is to present an in-depth numerical investigation on the statics of historical masonry stellar vaults, a special class of masonry ribbed vaults whose three-dimensional geometry features a star-shaped projection on the horizontal plane. In particular, the mechanical behavior of the masonry stellar vault belonging to the church of Santa Maria del Monte in Cagliari (Italy) is analyzed and illustrated as an especially meaningful case study. This church, which was built during the second half of the sixteenth century, is a beautiful example of Gothic-Catalan style, and its ribbed stellar vault is one of the most representative of this type in the town of Cagliari. The geometric outline of the vault has been obtained through laser scanning techniques and a procedure of reverse engineering. Starting from a three-dimensional representation of its geometry, the ultimate load-bearing capacity of the stellar vault can be accurately estimated through a recently developed, NURBS-based upper-bound limit analysis scheme. A comparison with incremental nonlinear analyses carried out with the commercial finite element code DIANA is presented. Furthermore, the paper also includes a sensitivity study aimed at investigating the role of ribs on the ultimate load-bearing capacity of the structure.
Journal Article
Material-Constructive Features and Structural Behavior of Sicilian Thin Shell Vaults
Thin-tile vaults, characterized by a wide variety of geometric configurations, represent an important part of the architectural heritage in Southern Italy. Many of these structures are still in serviceable condition. However, the absence of dedicated design guidelines and the need to comply with modern safety and serviceability requirements make their assessment and conservation a challenging task. The present study contributes to a more informed and responsible approach to these historic systems by addressing current normative limitations and by clarifying the structural role of construction elements such as counter-vaults and stiffening ribs. The research focuses on a representative case study located in Sicily, where this technique was extensively used from the late eighteenth century. The investigation combines direct on-site surveys, laboratory characterization of collected material samples, and numerical analysis based on finite-element elastic modeling. The results show that the traditional building knowledge, commonly described as the art of good manufacturing and transmitted through long-standing craftsmanship, produced a construction technique that still fulfills its structural function with remarkable effectiveness.
Journal Article
Brick Vaults by Slices in Choisy and Paredes
A brick barrel vault can be bonded basically according to three techniques depending on the arrangement of the bricks main planes: they can be radially orientated with respect to the vault axis (radial brick vault); they can be aligned with the vault surface (tile vault) or they can be vertical or slightly inclined, forming slices (vault by slices). The last two types do not require any formwork to be built. This work deals with the last case, vaults by slices, focusing on the study and comparison of two late nineteenth-century texts in France and Spain that go deeply into the geometry of this type of vault and still remain unstudied from this point of view: that of Choisy (Annales des Ponts et Chaussées 12: 439–449, 1876 and L’Art de bâtir chez les Byzantins. Librairie de la Société Anonyme de Publications Periodiques, Paris, 1883), who addresses the study of this type of vault in Byzantium, and that of Paredes (ca. 1883), who analyses the Spanish vault building tradition of this type in the region of Extremadura.
Journal Article