The formation of vault-tubes: a dynamic interaction between vaults and vault PARP

Zon, Arend van; Mossink, Marieke H.; Schoester, M.; Houtsmuller, Adriaan B.; Scheffer, George L.; Scheper, Rik J.; Sonneveld, Pieter; Wiemer, Erik A.C.

doi:10.1242/jcs.00749

Cited by 35 publications

(50 citation statements)

References 27 publications

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“…As you move outwards towards the cell periphery the number of MVP puncta diminishes. A similar staining pattern has been described with other MVP antibodies (Kedersha et al, 1990;Kickhoefer et al, 1999;van Zon et al, 2003). When potassium tellurite (K 2 TeO 3 ) is added to the culture medium, MVP is no longer concentrated near the nucleus.…”

Section: Mvp Aggregates Form In Response To Telluritesupporting

confidence: 75%

The major vault protein is related to the toxic anion resistance protein(TelA) family

Suprenant

Bloom

Fang

et al. 2007

Journal of Experimental Biology

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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 been identified. We used sequence analysis and molecular modeling to show that MVP and the toxic anion resistance protein, TelA of Rhodobacter sphaeroides strain 2.4.1,share a novel fold that consists of a three-stranded antiparallelβ-sheet. Because of this strong structural correspondence, we examined whether mammalian cell vaults respond to tellurite treatment. In the presence of the oxyanion tellurite, large vault aggregates, or vaultosomes, appear at the cell periphery in 15 min or less. Vaultosome formation is temperature-dependent, reversible, and occurs in normal human umbilical vein endothelial cells as well as transformed HeLa cervical cancer cells. Vaultosome formation is not restricted to tellurite and occurs in the presence of other toxic oxyanions (selenate, selinite, arsenate, arsenite, vanadate). In addition, vaultosomes form independently from other stress-induced ribonucleoprotein complexes, stress granules and aggresomes. Vaultosome formation is therefore a unique cellular response to an environmental toxin.

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Section: Mvp Aggregates Form In Response To Telluritesupporting

confidence: 75%

The major vault protein is related to the toxic anion resistance protein(TelA) family

Suprenant

Bloom

Fang

et al. 2007

Journal of Experimental Biology

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“…Two recent reports show the transport of MVP along microtubules (39,50). It is, however, important to note that all these studies have in common that it is just a smaller fraction of vaults that is found in these associations, and indeed, most vaults seem to freely diffuse in the cytoplasm at a rate that is consistent with their large size (27). We fail to see any gross disruptions of the microtubular network on MVP depletion, which argues that MVP does not influence its overall integrity.…”

Section: Discussionmentioning

confidence: 93%

“…MVP and MVP-green fluorescent protein (GFP) cDNA expression constructs were described elsewhere (27). Transfections were done as described previously (28).…”

Section: Methodsmentioning

confidence: 99%

“…The original MVP-GFP construct was previously shown to incorporate normally into vault particles (27) and mirror endogenous protein behavior. MVP-GFP was mutated at four silent positions at the target site for the siRNA construct (MVPmut-GFP), and polyclonal pools of UMUC-3 cells expressing MVPmut-GFP were generated by transfection followed by fluorescence-activated cell sorting.…”

Section: Mvp Is Necessary But Not Sufficient For Doxorubicin Resistanmentioning

confidence: 99%

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Depletion of major vault protein increases doxorubicin sensitivity and nuclear accumulation and disrupts its sequestration in lysosomes

Herlevsen

Oxford

Owens

et al. 2007

Molecular Cancer Therapeutics

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The major vault protein (MVP) is the major constituent of the vault particle, the largest known ribonuclear protein complex. To date, vaults have no clear function, although their low expression levels in de novo chemosensitive and curable tumors, such as testicular cancer, make them attractive candidates as contributors to intrinsic drug resistance. Here, we show that MVP knockdown in human bladder cancer cells via small interfering RNA results in sensitization toward doxorubicin in two distinct exposure protocols. The drug was detected in the nucleus immediately following addition and was subsequently sequestered to lysosomes, predominantly located adjacent to the nucleus. MVP knockdown leads to increased sensitivity toward doxorubicin and an enhanced nuclear accumulation of the drug as well as a loss of its perinuclear sequestration. Not only doxorubicin subcellular distribution was perturbed by MVP knockdown but lysosomal markers, such as pH-sensitive LysoSensor, pinocytosed dextran conjugates after 24-h chase period, and the lysosomal specific antigen Lamp-1, also showed a markedly different staining compared with controls. Lysosomes appeared dispersed through the cytoplasm without a clear organization adjacent to the nucleus. Microtubules, however, appeared unperturbed in cells with reduced MVP expression. Based on these data, we hypothesize that MVP and, by extension, vault complexes are important for lysosomal function and may influence cellular drug resistance by virtue of this role. [Mol Cancer Ther 2007;6(6):1804 -13]

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“…PARP-4 is incorporated into vaults, RNAcontaining subcellular particles in the cytoplasm [55]. Furthermore, ZAP, a human antiviral protein comprising a C-terminal PARP-like domain devoid of catalytic activity, has been shown to exhibit antiviral activity on alphaviruses [56], which contain an Xdomain similar to that of coronaviruses [23,27,28].…”

Section: Discussionmentioning

confidence: 99%

The SARS-Unique Domain (SUD) of SARS Coronavirus Contains Two Macrodomains That Bind G-Quadruplexes

Tan¹,

Hilgenfeld²

2009

SciVee

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Since the outbreak of severe acute respiratory syndrome (SARS) in 2003, the three-dimensional structures of several of the replicase/transcriptase components of SARS coronavirus (SARS-CoV), the non-structural proteins (Nsps), have been determined. However, within the large Nsp3 (1922 amino-acid residues), the structure and function of the so-called SARSunique domain (SUD) have remained elusive. SUD occurs only in SARS-CoV and the highly related viruses found in certain bats, but is absent from all other coronaviruses. Therefore, it has been speculated that it may be involved in the extreme pathogenicity of SARS-CoV, compared to other coronaviruses, most of which cause only mild infections in humans. In order to help elucidate the function of the SUD, we have determined crystal structures of fragment 389-652 (''SUD core '') of Nsp3, which comprises 264 of the 338 residues of the domain. Both the monoclinic and triclinic crystal forms (2.2 and 2.8 Å resolution, respectively) revealed that SUD core forms a homodimer. Each monomer consists of two subdomains, SUD-N and SUD-M, with a macrodomain fold similar to the SARS-CoV X-domain. However, in contrast to the latter, SUD fails to bind ADP-ribose, as determined by zone-interference gel electrophoresis. Instead, the entire SUD core as well as its individual subdomains interact with oligonucleotides known to form G-quadruplexes. This includes oligodeoxy-as well as oligoribonucleotides. Mutations of selected lysine residues on the surface of the SUD-N subdomain lead to reduction of Gquadruplex binding, whereas mutations in the SUD-M subdomain abolish it. As there is no evidence for Nsp3 entering the nucleus of the host cell, the SARS-CoV genomic RNA or host-cell mRNA containing long G-stretches may be targets of SUD. The SARS-CoV genome is devoid of G-stretches longer than 5-6 nucleotides, but more extended G-stretches are found in the 39-nontranslated regions of mRNAs coding for certain host-cell proteins involved in apoptosis or signal transduction, and have been shown to bind to SUD in vitro. Therefore, SUD may be involved in controlling the host cell's response to the viral infection. Possible interference with poly(ADP-ribose) polymerase-like domains is also discussed.

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The formation of vault-tubes: a dynamic interaction between vaults and vault PARP

Cited by 35 publications

References 27 publications

The major vault protein is related to the toxic anion resistance protein(TelA) family

The major vault protein is related to the toxic anion resistance protein(TelA) family

Depletion of major vault protein increases doxorubicin sensitivity and nuclear accumulation and disrupts its sequestration in lysosomes

The SARS-Unique Domain (SUD) of SARS Coronavirus Contains Two Macrodomains That Bind G-Quadruplexes

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