vault ribonucleoprotein particles

Summary

Summary: Large cytoplasmic ribonucleoprotein particles that have an eight-fold symmetry with a central pore and petal-like structure giving the appearance of an octagonal dome. (The Dictionary of Cell Biology, Lackie and Dow, 2nd ed.)

Top Publications

  1. Izquierdo M, Scheffer G, Flens M, Giaccone G, Broxterman H, Meijer C, et al. Broad distribution of the multidrug resistance-related vault lung resistance protein in normal human tissues and tumors. Am J Pathol. 1996;148:877-87 pubmed
  2. Yang J, Kickhoefer V, Ng B, Gopal A, Bentolila L, John S, et al. Vaults are dynamically unconstrained cytoplasmic nanoparticles capable of half vault exchange. ACS Nano. 2010;4:7229-40 pubmed publisher
    ..This data suggests a means whereby vaults can functionally interact with their cellular environment and deliver materials packaged within their interior...
  3. Tanaka H, Kato K, Yamashita E, Sumizawa T, Zhou Y, Yao M, et al. The structure of rat liver vault at 3.5 angstrom resolution. Science. 2009;323:384-8 pubmed publisher
    ..Interactions between the 42-turn-long cap-helix domains are key to stabilizing the particle. The shoulder domain is structurally similar to a core domain of stomatin, a lipid-raft component in erythrocytes and epithelial cells...
  4. Paspalas C, Perley C, Venkitaramani D, Goebel Goody S, Zhang Y, Kurup P, et al. Major vault protein is expressed along the nucleus-neurite axis and associates with mRNAs in cortical neurons. Cereb Cortex. 2009;19:1666-77 pubmed publisher
    ..Taken together, our findings provide the first characterization of neuronal MVP along the nucleus-neurite axis and may offer new insights into its possible function(s) in the brain...
  5. Saglam A, Hayran M, Uner A. Immunohistochemical expression of multidrug resistance proteins in mature T/NK-cell lymphomas. APMIS. 2008;116:791-800 pubmed
    ..We detected P-gp expression in 31% (13/42), MRP-1 expression in 74% (31/42), BCRP in 78% (32/41) and LRP in 59% (26/44) of the cases. These findings show that our T/NK-cell lymphoma cases display high frequency of MDR protein expression...
  6. Berger W, Steiner E, Grusch M, Elbling L, Micksche M. Vaults and the major vault protein: novel roles in signal pathway regulation and immunity. Cell Mol Life Sci. 2009;66:43-61 pubmed publisher
    ..Here we review the current knowledge on MVP and vaults with focus on regulatory functions in intracellular signal transduction and immune defence...
  7. Kowalski M, Dubouix Bourandy A, Bajmoczi M, Golan D, Zaidi T, Coutinho Sledge Y, et al. Host resistance to lung infection mediated by major vault protein in epithelial cells. Science. 2007;317:130-2 pubmed
    ..MVP was also essential for optimal epithelial cell internalization and clearance of P. aeruginosa. These results suggest that MVP makes a substantial contribution to epithelial cell-mediated resistance to infection...
  8. Mandoky L, Geczi L, Doleschall Z, Bodrogi I, Csuka O, Kasler M, et al. Expression and prognostic value of the lung resistance-related protein (LRP) in germ cell testicular tumors. Anticancer Res. 2004;24:1097-104 pubmed
    ..The aim of this study was to evaluate the expression of LRP in germ cell testicular tumors (GCT) and to determine the correlation between LRP expression and the clinical outcome of these tumors...
  9. Mossink M, van Zon A, Scheper R, Sonneveld P, Wiemer E. Vaults: a ribonucleoprotein particle involved in drug resistance?. Oncogene. 2003;22:7458-67 pubmed
    ..Here, we review the current knowledge on the vault complex and critically discuss the evidence that links vaults to drug resistance...

More Information

Publications62

  1. Kickhoefer V, Liu Y, Kong L, Snow B, Stewart P, Harrington L, et al. The Telomerase/vault-associated protein TEP1 is required for vault RNA stability and its association with the vault particle. J Cell Biol. 2001;152:157-64 pubmed
    ..Therefore, we have uncovered a novel role for TEP1 in vivo as an integral vault protein important for the stabilization and recruitment of the vault RNA to the vault particle...
  2. Hamill D, Suprenant K. Characterization of the sea urchin major vault protein: a possible role for vault ribonucleoprotein particles in nucleocytoplasmic transport. Dev Biol. 1997;190:117-28 pubmed
    ..Based on their copurification and intracellular distribution, vaults may be involved in the nucleocytoplasmic transport of ribosomes and/or mRNA...
  3. Rimsza L, Campbell K, Dalton W, Salmon S, Willcox G, Grogan T. The major vault protein (MVP), a new multidrug resistance associated protein, is frequently expressed in multiple myeloma. Leuk Lymphoma. 1999;34:315-24 pubmed
    ..0002). The collective work indicates that MVP protein is common and abundant in myeloma with potential relevance to therapeutic response...
  4. Dingemans A, van Ark Otte J, van der Valk P, Apolinario R, Scheper R, Postmus P, et al. Expression of the human major vault protein LRP in human lung cancer samples and normal lung tissues. Ann Oncol. 1996;7:625-30 pubmed
    ..The recently discovered LRP protein has been shown to be involved in drug resistance and possibly in detoxification processes...
  5. Kong L, Siva A, Kickhoefer V, Rome L, Stewart P. RNA location and modeling of a WD40 repeat domain within the vault. RNA. 2000;6:890-900 pubmed
    ..The molecular architecture of the complex is emerging, with 96 copies of MVP composing the eightfold symmetric barrel, and the vRNA together with one copy of TEP1 and four predicted copies of VPARP comprising each cap...
  6. Kickhoefer V, Rome L. The sequence of a cDNA encoding the major vault protein from Rattus norvegicus. Gene. 1994;151:257-60 pubmed
    ..Comparison of the deduced amino acid (aa) sequence to that of MvpA from Dictyostelium discoideum revealed that the proteins share about 57% aa identity. Southern blot analysis indicates that the rat MVP is a single-copy gene...
  7. Kickhoefer V, Rajavel K, Scheffer G, Dalton W, Scheper R, Rome L. Vaults are up-regulated in multidrug-resistant cancer cell lines. J Biol Chem. 1998;273:8971-4 pubmed
    ..The observation that vault synthesis is linked directly to multidrug resistance supports a direct role for vaults in drug resistance...
  8. Ryu S, An H, Oh Y, Choi H, Ha M, Park S. On the role of major vault protein in the resistance of senescent human diploid fibroblasts to apoptosis. Cell Death Differ. 2008;15:1673-80 pubmed publisher
    ..Taken together, these results suggest that MVP is important in the resistance of senescent HDFs to apoptosis by modulation of Bcl-2 expression by JNK pathway...
  9. Ryu S, Park S. Targeting major vault protein in senescence-associated apoptosis resistance. Expert Opin Ther Targets. 2009;13:479-84 pubmed
  10. Gopinath S, Matsugami A, Katahira M, Kumar P. Human vault-associated non-coding RNAs bind to mitoxantrone, a chemotherapeutic compound. Nucleic Acids Res. 2005;33:4874-81 pubmed
    ..Taken together, our results clearly suggest that vRNAs have the ability to bind certain chemotherapeutic compounds and these interactions may play an important role in vault function, by participating in the export of toxic compounds...
  11. Qadir M, O Loughlin K, Fricke S, Williamson N, Greco W, Minderman H, et al. Cyclosporin A is a broad-spectrum multidrug resistance modulator. Clin Cancer Res. 2005;11:2320-6 pubmed
    ..Cyclosporin A is known to also modulate MRP-1, and we hypothesized that broad-spectrum multidrug resistance modulation might contribute to its clinical efficacy...
  12. Kickhoefer V, Garcia Y, Mikyas Y, Johansson E, Zhou J, Raval Fernandes S, et al. Engineering of vault nanocapsules with enzymatic and fluorescent properties. Proc Natl Acad Sci U S A. 2005;102:4348-52 pubmed
    ..The modified vaults are compatible with living cells. The ability to engineer vault particles with designed properties and functionalities represents an important step toward development of a biocompatible nanocapsule...
  13. Wang W, Ke S, Chen G, Gao Q, Wu S, Wang S, et al. Effect of lung resistance-related protein on the resistance to cisplatin in human ovarian cancer cell lines. Oncol Rep. 2004;12:1365-70 pubmed
    ..Thus, LRP was involved in the resistance of ovarian cancer cells to cisplatin and has an important role in the transport of cisplatin both in exocytotic vesicles and between the nucleus and cytoplasm...
  14. Valera E, Scrideli C, Queiroz R, Mori B, Tone L. Multiple drug resistance protein (MDR-1), multidrug resistance-related protein (MRP) and lung resistance protein (LRP) gene expression in childhood acute lymphoblastic leukemia. Sao Paulo Med J. 2004;122:166-71 pubmed
    ..Expression of genes for the multiple drug resistance protein (MDR-1), multidrug resistance-related protein (MRP), and lung resistance protein (LRP) may confer the phenotype of resistance to the treatment of neoplasias...
  15. Iwashita K, Ikeda R, Takeda Y, Sumizawa T, Furukawa T, Yamaguchi T, et al. Major vault protein forms complexes with hypoxia-inducible factor (HIF)-1alpha and reduces HIF-1alpha level in ACHN human renal adenocarcinoma cells. Cancer Sci. 2010;101:920-6 pubmed publisher
    ..Taken together, these results suggest that vaults function as scaffolds in HIF-1alpha degradation pathway and promote the ubiquitination and degradation of HIF-1alpha...
  16. Fichtner I, Paal K, Borgmann A, Badiali L, Wurm R, Henze G. Chemo- and radiation sensitivity of xenografted acute lymphoblastic leukemias--correlation to the expression of multidrug resistance proteins. Anticancer Res. 2003;23:2657-64 pubmed
    ..We conclude that in the drug resistance phenotype of ALL not only the above mentioned proteins but a variety of different molecules are involved...
  17. Sunnaram B, Gandemer V, Sebillot M, Grandgirard N, Amiot L, Leray E, et al. LRP overexpression in monocytic lineage. Leuk Res. 2003;27:755-9 pubmed
    ..In conclusion, we report that LRP is rather a marker of monocytic lineage than a prognostic index for MDR and we suggest that detection of LRP by ICC could be an argument for the diagnosis of monoblastic and monocytic leukemias...
  18. Kickhoefer V, Poderycki M, Chan E, Rome L. The La RNA-binding protein interacts with the vault RNA and is a vault-associated protein. J Biol Chem. 2002;277:41282-6 pubmed
    ..Moreover, we also demonstrate that the La autoantigen is the 50-kDa protein that we have previously reported as a protein that co-purifies with vaults...
  19. Yu Z, Fotouhi Ardakani N, Wu L, Maoui M, Wang S, Banville D, et al. PTEN associates with the vault particles in HeLa cells. J Biol Chem. 2002;277:40247-52 pubmed
    ..Furthermore, the in vitro binding experiments revealed that the interaction of PTEN with MVP is Ca(2+)-dependent...
  20. Siva A, Raval Fernandes S, Stephen A, LaFemina M, Scheper R, Kickhoefer V, et al. Up-regulation of vaults may be necessary but not sufficient for multidrug resistance. Int J Cancer. 2001;92:195-202 pubmed
    ..This implies a requirement of an additional factor(s) for vault-mediated MDR...
  21. Pohl G, Suchomel R, Stranzl T, Depisch D, Stiglbauer W, Filipits M, et al. Expression of the lung resistance protein in primary colorectal carcinomas. Anticancer Res. 2001;21:201-4 pubmed
    ..However, patients with high LRP expression in their carcinomas had a prolonged survival. Thus LRP is frequently expressed in colorectal carcinomas and high expression might indicate improved survival...
  22. van Zon A, Mossink M, Schoester M, Scheffer G, Scheper R, Sonneveld P, et al. Structural domains of vault proteins: a role for the coiled coil domain in vault assembly. Biochem Biophys Res Commun. 2002;291:535-41 pubmed
    ..However, the N-terminal half of MVP binds to a specific domain in the C-terminus of VPARP. Furthermore, VPARP contains amino acid stretches mediating intramolecular binding...
  23. Suprenant K. Vault ribonucleoprotein particles: sarcophagi, gondolas, or safety deposit boxes?. Biochemistry. 2002;41:14447-54 pubmed
  24. Huffman K, Corey D. Major vault protein does not play a role in chemoresistance or drug localization in a non-small cell lung cancer cell line. Biochemistry. 2005;44:2253-61 pubmed
    ..Our results suggest the need for further investigation into the link between upregulation of vaults and malignancy, the mechanism behind non-P-gp-mediated drug resistance, and the role of vaults in human cells...
  25. Lange C, Walther W, Schwabe H, Stein U. Cloning and initial analysis of the human multidrug resistance-related MVP/LRP gene promoter. Biochem Biophys Res Commun. 2000;278:125-33 pubmed
    ..The promoter is TATA-less and contains an inverted CCAAT-box and a Sp1 site located near to a p53 binding motif. An alternative 3'-splice site of intron 1 results in a splicing variant within the 5'-untranslated region of MVP mRNA...
  26. Mayr D, Pannekamp U, Baretton G, Gropp M, Meier W, Flens M, et al. Immunohistochemical analysis of drug resistance-associated proteins in ovarian carcinomas. Pathol Res Pract. 2000;196:469-75 pubmed
    ..Our observations confirm the prognostic significance of p53 accumulation in ovarian carcinomas. Only GSTpi immunoreactivity was significantly correlated with drug resistance...
  27. Kim E, Lee S, Mian M, Yun S, Song M, Yi K, et al. Crosstalk between Src and major vault protein in epidermal growth factor-dependent cell signalling. FEBS J. 2006;273:793-804 pubmed
    ..To our knowledge, this is the first report of MVP interacting with a protein tyrosine kinase involved in a distinct cell signalling pathway. It appears that MVP is a novel regulator of Src-mediated signalling cascades...
  28. Kanzaki A, Toi M, Nakayama K, Bando H, Mutoh M, Uchida T, et al. Expression of multidrug resistance-related transporters in human breast carcinoma. Jpn J Cancer Res. 2001;92:452-8 pubmed
    ..P-glycoprotein (P-gp) / MDR1, MRP1 and LRP may play more important roles than BCRP in chemotherapy of human breast carcinoma...
  29. Chung J, Ginn Pease M, Eng C. Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) has nuclear localization signal-like sequences for nuclear import mediated by major vault protein. Cancer Res. 2005;65:4108-16 pubmed
    ..Further, we show that this MVP-mediated nuclear import is independent of PTEN phosphorylation and of the lipid and protein phosphatase activities of PTEN...
  30. Schroeijers A, Scheffer G, Reurs A, Pijnenborg A, Abbondanza C, Wiemer E, et al. Detection of the Mr 110,000 lung resistance-related protein LRP/MVP with monoclonal antibodies. J Histochem Cytochem. 2001;49:1379-85 pubmed
    ..The availability of a broader panel of reagents for the specific and sensitive immunodetection of LRP/MVP should greatly facilitate biological and clinical studies of vault-related MDR...
  31. Schroeijers A, Reurs A, Scheffer G, Stam A, de Jong M, Rustemeyer T, et al. Up-regulation of drug resistance-related vaults during dendritic cell development. J Immunol. 2002;168:1572-8 pubmed
    ..These data point to a role for vaults in both DC survival and functioning as APC...
  32. van Zon A, Mossink M, Schoester M, Scheper R, Sonneveld P, Wiemer E. Efflux kinetics and intracellular distribution of daunorubicin are not affected by major vault protein/lung resistance-related protein (vault) expression. Cancer Res. 2004;64:4887-92 pubmed
    ..Our results indicate that vaults are not directly involved in the sequestration of anthracyclines in vesicles nor in their efflux from the nucleus...
  33. Cheng S, Lam W, Lee A, Fung K, Wu R, Fong W. Low-level doxorubicin resistance in benzo[a]pyrene-treated KB-3-1 cells is associated with increased LRP expression and altered subcellular drug distribution. Toxicol Appl Pharmacol. 2000;164:134-42 pubmed
    ..These results also propose an alternative mechanism of cancer drug resistance emergence, namely, induction of LRP activity following treatment with BaP, an environmental toxicant and a carcinogen...
  34. Kolli S, Zito C, Mossink M, Wiemer E, Bennett A. The major vault protein is a novel substrate for the tyrosine phosphatase SHP-2 and scaffold protein in epidermal growth factor signaling. J Biol Chem. 2004;279:29374-85 pubmed
    ..We propose that MVP functions as a novel scaffold protein for both SHP-2 and Erk. The regulation of MVP tyrosyl phosphorylation by SHP-2 may play an important role in cell survival signaling...
  35. Chiou J, Liang J, Hsu W, Wang J, Ho S, Kao A. Comparing the relationship of Taxol-based chemotherapy response with P-glycoprotein and lung resistance-related protein expression in non-small cell lung cancer. Lung. 2003;181:267-73 pubmed
    ..We concluded that Taxol-based chemotherapy response of patients with NSCLC was related to Pgp but not LPR expression...
  36. Harada T, Ogura S, Yamazaki K, Kinoshita I, Itoh T, Isobe H, et al. Predictive value of expression of P53, Bcl-2 and lung resistance-related protein for response to chemotherapy in non-small cell lung cancers. Cancer Sci. 2003;94:394-9 pubmed
    ..These findings indicate that immunostaining for P53 and LRP using TBB specimens may be useful for dividing patients with NSCLC into chemoresponsive and chemoresistant groups...
  37. Hu Y, Stephen A, Cao J, Tanzer L, Slapak C, Harrison S, et al. A very early induction of major vault protein accompanied by increased drug resistance in U-937 cells. Int J Cancer. 2002;97:149-56 pubmed
    ..In summary, U-937 doxorubicin-selected cells are programmed to rapidly upregulate MVP mRNA levels, to accumulate vault particles and to become multidrug resistant...
  38. Liu Y, Snow B, Kickhoefer V, Erdmann N, Zhou W, Wakeham A, et al. Vault poly(ADP-ribose) polymerase is associated with mammalian telomerase and is dispensable for telomerase function and vault structure in vivo. Mol Cell Biol. 2004;24:5314-23 pubmed
    ..These data suggest that murine mTep1 and mVparp, alone or in combination, are dispensable for normal development, telomerase catalysis, telomere length maintenance, and vault structure in vivo...
  39. Stephen A, Raval Fernandes S, Huynh T, Torres M, Kickhoefer V, Rome L. Assembly of vault-like particles in insect cells expressing only the major vault protein. J Biol Chem. 2001;276:23217-20 pubmed
    ..Understanding vault assembly will enable us to design agents that disrupt vault formation and hence aid in elucidating vault function in vivo...
  40. Sauerbrey A, Voigt A, Wittig S, Häfer R, Zintl F. Messenger RNA analysis of the multidrug resistance related protein (MRP1) and the lung resistance protein (LRP) in de novo and relapsed childhood acute lymphoblastic leukemia. Leuk Lymphoma. 2002;43:875-9 pubmed
    ..12 and for MRPI: p = 0.95), however, patients who showed high LRP expression exhibited a lower tendency of remaining in continuous first remission...
  41. Ikeda K, Oka M, Yamada Y, Soda H, Fukuda M, Kinoshita A, et al. Adult T-cell leukemia cells over-express the multidrug-resistance-protein (MRP) and lung-resistance-protein (LRP) genes. Int J Cancer. 1999;82:599-604 pubmed
    ..Our findings suggest that the MRP and LRP genes in ATL are often activated by HTLV-I infection and may confer MDR of ATL cells in vivo. Combined chemotherapy with inhibitors of these MDR genes may be promising in the treatment of ATL...
  42. Lara P, Lloret M, Clavo B, Apolinario R, Henríquez Hernández L, Bordon E, et al. Severe hypoxia induces chemo-resistance in clinical cervical tumors through MVP over-expression. Radiat Oncol. 2009;4:29 pubmed publisher
  43. Henríquez Hernández L, Lloret M, Pinar B, Bordon E, Rey A, Lubrano A, et al. BCL-2, in combination with MVP and IGF-1R expression, improves prediction of clinical outcome in complete response cervical carcinoma patients treated by radiochemotherapy. Gynecol Oncol. 2011;122:585-9 pubmed publisher
    ..To investigate whether BCL-2 expression would improve MVP/IGF-1R prediction of clinical outcome in cervix carcinoma patients treated by radiochemotherapy, and suggest possible mechanisms behind this effect...
  44. Lara P, Pruschy M, Zimmermann M, Henríquez Hernández L. MVP and vaults: a role in the radiation response. Radiat Oncol. 2011;6:148 pubmed publisher
    ..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...
  45. Bottke D, Koychev D, Busse A, Heufelder K, Wiegel T, Thiel E, et al. Fractionated irradiation can induce functionally relevant multidrug resistance gene and protein expression in human tumor cell lines. Radiat Res. 2008;170:41-8 pubmed publisher
  46. Kozlov G, Vavelyuk O, Minailiuc O, Banville D, Gehring K, Ekiel I. Solution structure of a two-repeat fragment of major vault protein. J Mol Biol. 2006;356:444-52 pubmed
    ..Chemical shift perturbation studies identified the binding site of vault poly(ADP-ribose) polymerase, another component of vault particles, indicating that MVP domains form a new class of interaction-mediating modules...
  47. Raval Fernandes S, Kickhoefer V, Kitchen C, Rome L. Increased susceptibility of vault poly(ADP-ribose) polymerase-deficient mice to carcinogen-induced tumorigenesis. Cancer Res. 2005;65:8846-52 pubmed
    ..The increase in carcinogen-induced tumors in VPARP-deficient mice is the only phenotype observed to date, and suggests a possible role for VPARP, directly or indirectly, in chemically induced neoplasia...
  48. Querol Audi J, Perez Luque R, Fita I, Lopez Iglesias C, Castón J, Carrascosa J, et al. Preliminary analysis of two and three dimensional crystals of vault ribonucleoprotein particles. J Struct Biol. 2005;151:111-5 pubmed
    ..Compatibility with the reported 8-fold symmetry would imply multiples of 24-fold rotational symmetry, in agreement with the recently proposed 48-fold dihedral symmetry for reconstituted recombinant vaults...
  49. Kitazono M, Okumura H, Ikeda R, Sumizawa T, Furukawa T, Nagayama S, et al. Reversal of LRP-associated drug resistance in colon carcinoma SW-620 cells. Int J Cancer. 2001;91:126-31 pubmed
    ..These findings suggest that at least in part, PAK-104P reverses LRP-mediated drug resistance by inhibiting the efflux of ADM from nuclei. PAK-104P may be useful for reversing MDR in tumors that overexpress LRP...
  50. Lloret M, Lara P, Bordon E, Fontes F, Rey A, Pinar B, et al. Major vault protein may affect nonhomologous end-joining repair and apoptosis through Ku70/80 and bax downregulation in cervical carcinoma tumors. Int J Radiat Oncol Biol Phys. 2009;73:976-9 pubmed publisher
  51. Diestra J, Condom E, del Muro X, Scheffer G, Perez J, Zurita A, et al. Expression of multidrug resistance proteins P-glycoprotein, multidrug resistance protein 1, breast cancer resistance protein and lung resistance related protein in locally advanced bladder cancer treated with neoadjuvant chemotherapy: biological and . J Urol. 2003;170:1383-7 pubmed
  52. Burger H, Foekens J, Look M, Meijer van Gelder M, Klijn J, Wiemer E, et al. RNA expression of breast cancer resistance protein, lung resistance-related protein, multidrug resistance-associated proteins 1 and 2, and multidrug resistance gene 1 in breast cancer: correlation with chemotherapeutic response. Clin Cancer Res. 2003;9:827-36 pubmed
    ..The aim of this study was to investigate whether expression of particular drug resistance genes in primary operable breast cancer correlates with response to first-line chemotherapy in advanced disease...
  53. van den Heuvel Eibrink M, Wiemer E, Prins A, Meijerink J, Vossebeld P, van der Holt B, et al. Increased expression of the breast cancer resistance protein (BCRP) in relapsed or refractory acute myeloid leukemia (AML). Leukemia. 2002;16:833-9 pubmed
    ..A significant co-expression of BCRP and MDR1 was found at diagnosis (r = 0.47, P = 0.04). The present results suggest that BCRP, but not MDR1, MRP1 or LRP/MVP is associated with clinical resistant disease in AML...