Vaults and the major vault protein: Novel roles in signal pathway regulation and immunity

  title={Vaults and the major vault protein: Novel roles in signal pathway regulation and immunity},
  author={Walter Berger and Elisabeth Steiner and Michael Grusch and Leonilla Elbling and Michael Micksche},
  journal={Cellular and Molecular Life Sciences},
Abstract.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… 
MVP and vaults: a role in the radiation response
New roles have been assigned to MVP and vaults including the association with the insulin-like growth factor-1, hypoxia-induciblefactor-1alpha, and the two major DNA double-strand break repair machineries: non-homologous endjoining and homologous recombination.
Expression of the Major Vault Protein (MVP) and Cellular Vault Particles in Fish
It is shown that vaults are distributed throughout cells of fish lymphoid cells, with nuclear and plasma membrane aggregations in some cells, and MVP is highly expressed in liver neoplastic lesions in Atlantic killifish collected at the Atlantic Wood USA‐EPA superfund site on the southern branch of the Elizabeth River, VA.
Structural Dynamics of the Vault Ribonucleoprotein Particle
The high resolution, crystal structure of the of the seven N-terminal domains of MVP, forming the central vault barrel, revealed the interactions governing vault association and suggested a pH-dependent mechanism for a reversible dissociation induced by low pH.
The mechanism of vault opening from the high resolution structure of the N-terminal repeats of MVP
The crystal structure of the vault particle solved at 8 Å resolution, together with the 7 N‐terminal domains of MVP, reveal the interactions governing vault association and provide an explanation for a reversible dissociation induced by low pH.
Small but Powerful: The Human Vault RNAs as Multifaceted Modulators of Pro-Survival Characteristics and Tumorigenesis
The identified and known functions of the human vault RNAs in the context of cell proliferation, tumorigenesis and chemotherapy resistance are discussed.
Bacterial Major Vault Protein homologs shed new light on origins of the enigmatic organelle
It is speculated that the most likely scenario for vault appearance in eukaryotes is horizontal gene transfer from cyanobacteria, and it was shown that MVP sequences from chemotrophic bacteria Myxococcales and Cytophagales contain a domain homologous to Eukaryotic band-7 domain, unlike cyanobacterial and eukARYotic major vault proteins.
Vault RNAs: hidden gems in RNA and protein regulation
Vault RNAs are largely unknown and their molecular role is still under investigation, but their involvement in cellular mechanisms are summarized.
Novel Molecular Basis for Synapse Formation: Small Non-coding Vault RNA Functions as a Riboregulator of MEK1 to Modulate Synaptogenesis
The regulatory mechanism of MAPK signaling in synaptogenesis by vtRNAs is introduced and the possibility as a novel molecular basis for synapse formation is discussed.


Cellular functions of vaults and their involvement in multidrug resistance.
The finding that MVP binds several phosphatases and kinases including PTEN, SHP-2 as well as Erk suggests that MVP might be involved in the regulation of important cell signalling pathways including the PI3K/Akt and the MAPK pathways.
Up‐regulation of vaults may be necessary but not sufficient for multidrug resistance
It is demonstrated that while vault levels may be a good predictor of drug resistance, their up‐regulation alone is not sufficient to confer the drug‐resistant phenotype, which implies a requirement of an additional factor(s) for vault‐mediated MDR.
The major vault protein is related to the toxic anion resistance protein (TelA) family
SUMMARY Vaults are barrel-shaped ribonucleoprotein particles that are abundant in certain tumors and multidrug resistant cancer cells. Prokaryotic relatives of the major vault protein, MVP, have not
The formation of vault-tubes: a dynamic interaction between vaults and vault PARP
The subcellular localization and the dynamics of the vault complex in a non-small cell lung cancer cell line expressing MVP tagged with green fluorescent protein indicate a direct and dynamic relationship between vaults and VPARP, providing further clues to unravel the function of vaults.
Characterization of MVP and VPARP assembly into vault ribonucleoprotein complexes.
Vaults: a ribonucleoprotein particle involved in drug resistance?
The hollow barrel-shaped structure of the vault complex and its subcellular localization indicate a function in intracellular transport, and it was postulated that vaults contributed to drug resistance by transporting drugs away from their intrACEllular targets and/or the sequestration of drugs.
RNA location and modeling of a WD40 repeat domain within the vault.
To locate the position of the vRNA, vaults were treated with RNases, and cryo-electron microscopy was performed on the resulting complexes, revealing the v RNA to be at the ends of the vault caps.
Structural domains of vault proteins: a role for the coiled coil domain in vault assembly.
This study identified and analyzed structural domains involved in vault assembly with emphasis on protein-protein interactions and demonstrated within MVP an intramolecular binding site and show that MVP molecules interact with each other via their coiled coil domain.
Multiple Human Vault RNAs
The findings suggest that vaults bind the RNA molecules with different affinities in different situations, and the ratio in which the vault RNAs are associated with vaults might be of functional importance.