Major vault protein explained

Major vault protein, also known as lung resistance-related protein is a protein that in humans is encoded by the MVP gene.^[1] 78 copies of the protein assemble into the large compartments called vaults.

Function

This gene encodes the major vault protein which is a lung infection resistance-related protein. Vaults are multi-subunit structures that may be involved in nucleo-cytoplasmic transport. Major vault protein comprises 70% of vaults which also contain vPARP and TEP1.^[2] This protein mediates drug resistance, perhaps via a transport process. It is widely distributed in normal tissues and overexpressed in multidrug-resistant cancer cells. The protein overexpression is a potentially useful marker of clinical drug resistance. This gene produces two transcripts by using two alternative exon 2 sequences; however, the open reading frames are the same in both transcripts.^[3]

Interactions

Major vault protein coimmunoprecipitates with the human estrogen receptor and treatment with estradiol increases major vault protein associated with the estrogen receptor in nuclear extracts.^[4]

Major vault protein has been shown to interact with estrogen receptor alpha,^[5] PTEN^[6] and PARP4.^{[7] [8]}

Further reading

• Izquierdo MA, Scheffer GL, Flens MJ, Schroeijers AB, van der Valk P, Scheper RJ . Major vault protein LRP-related multidrug resistance . European Journal of Cancer . 32A . 6 . 979–984 . June 1996 . 8763338 . 10.1016/0959-8049(96)00053-6 .
• Slovak ML, Ho JP, Cole SP, Deeley RG, Greenberger L, de Vries EG, Broxterman HJ, Scheffer GL, Scheper RJ . The LRP gene encoding a major vault protein associated with drug resistance maps proximal to MRP on chromosome 16: evidence that chromosome breakage plays a key role in MRP or LRP gene amplification . Cancer Research . 55 . 19 . 4214–4219 . October 1995 . 7671223 .
• Izquierdo MA, Scheffer GL, Flens MJ, Giaccone G, Broxterman HJ, Meijer CJ, van der Valk P, Scheper RJ . Broad distribution of the multidrug resistance-related vault lung resistance protein in normal human tissues and tumors . The American Journal of Pathology . 148 . 3 . 877–887 . March 1996 . 8774142 . 1861735 .
• Dingemans AM, van Ark-Otte J, van der Valk P, Apolinario RM, Scheper RJ, Postmus PE, Giaccone G . Expression of the human major vault protein LRP in human lung cancer samples and normal lung tissues . Annals of Oncology . 7 . 6 . 625–630 . August 1996 . 8879378 . 10.1093/oxfordjournals.annonc.a010681 . free .
• Sugawara I, Akiyama S, Scheper RJ, Itoyama S . Lung resistance protein (LRP) expression in human normal tissues in comparison with that of MDR1 and MRP . Cancer Letters . 112 . 1 . 23–31 . January 1997 . 9029166 . 10.1016/S0304-3835(96)04542-9 .
• Abbondanza C, Rossi V, Roscigno A, Gallo L, Belsito A, Piluso G, Medici N, Nigro V, Molinari AM, Moncharmont B, Puca GA . Interaction of vault particles with estrogen receptor in the MCF-7 breast cancer cell . The Journal of Cell Biology . 141 . 6 . 1301–1310 . June 1998 . 9628887 . 2132791 . 10.1083/jcb.141.6.1301 .
• Ikeda K, Oka M, Yamada Y, Soda H, Fukuda M, Kinoshita A, Tsukamoto K, Noguchi Y, Isomoto H, Takeshima F, Murase K, Kamihira S, Tomonaga M, Kohno S . Adult T-cell leukemia cells over-express the multidrug-resistance-protein (MRP) and lung-resistance-protein (LRP) genes . International Journal of Cancer . 82 . 4 . 599–604 . August 1999 . 10404077 . 10.1002/(SICI)1097-0215(19990812)82:4<599::AID-IJC21>3.0.CO;2-R . 20438112 .
• Rimsza LM, Campbell K, Dalton WS, Salmon S, Willcox G, Grogan TM . The major vault protein (MVP), a new multidrug resistance associated protein, is frequently expressed in multiple myeloma . Leukemia & Lymphoma . 34 . 3–4 . 315–324 . July 1999 . 10439368 . 10.3109/10428199909050956 .
• Kickhoefer VA, Siva AC, Kedersha NL, Inman EM, Ruland C, Streuli M, Rome LH . The 193-kD vault protein, VPARP, is a novel poly(ADP-ribose) polymerase . The Journal of Cell Biology . 146 . 5 . 917–928 . September 1999 . 10477748 . 2169495 . 10.1083/jcb.146.5.917 .
• Kickhoefer VA, Stephen AG, Harrington L, Robinson MO, Rome LH . Vaults and telomerase share a common subunit, TEP1 . The Journal of Biological Chemistry . 274 . 46 . 32712–32717 . November 1999 . 10551828 . 10.1074/jbc.274.46.32712 . free .
• Lange C, Walther W, Schwabe H, Stein U . Cloning and initial analysis of the human multidrug resistance-related MVP/LRP gene promoter . Biochemical and Biophysical Research Communications . 278 . 1 . 125–133 . November 2000 . 11071864 . 10.1006/bbrc.2000.3782 .
• Holzmann K, Ambrosch I, Elbling L, Micksche M, Berger W . A small upstream open reading frame causes inhibition of human major vault protein expression from a ubiquitous mRNA splice variant . FEBS Letters . 494 . 1–2 . 99–104 . April 2001 . 11297743 . 10.1016/S0014-5793(01)02318-3 . 9235641 . free . 2001FEBSL.494...99H .
• van Zon A, Mossink MH, Schoester M, Scheffer GL, Scheper RJ, Sonneveld P, Wiemer EA . Structural domains of vault proteins: a role for the coiled coil domain in vault assembly . Biochemical and Biophysical Research Communications . 291 . 3 . 535–541 . March 2002 . 11855821 . 10.1006/bbrc.2002.6472 .
• Sakaki Y, Terashi K, Yamaguchi A, Kawamata N, Tokito Y, Mori H, Umehara M, Yoshiyama T, Ohtsubo H, Arimura K, Arima N, Tei C . Human T-cell lymphotropic virus type I Tax activates lung resistance-related protein expression in leukemic clones established from an adult T-cell leukemia patient . Experimental Hematology . 30 . 4 . 340–345 . April 2002 . 11937269 . 10.1016/S0301-472X(02)00775-0 . free .
• Zhao Y, Yu L, Wang Q, Lou F, Pu J . [The relationship between expression of lung resistance-related protein gene or multidrug resistance-associated protein gene and prognosis in newly diagnosed acute leukemia] . Zhonghua Nei Ke Za Zhi . 41 . 3 . 183–185 . March 2002 . 11940320 .
• Scheffer GL, Pijnenborg AC, Smit EF, Müller M, Postma DS, Timens W, van der Valk P, de Vries EG, Scheper RJ . Multidrug resistance related molecules in human and murine lung . Journal of Clinical Pathology . 55 . 5 . 332–339 . May 2002 . 11986335 . 1769658 . 10.1136/jcp.55.5.332 .
• van den Heuvel-Eibrink MM, Wiemer EA, Prins A, Meijerink JP, Vossebeld PJ, van der Holt B, Pieters R, Sonneveld P . Increased expression of the breast cancer resistance protein (BCRP) in relapsed or refractory acute myeloid leukemia (AML) . Leukemia . 16 . 5 . 833–839 . May 2002 . 11986944 . 10.1038/sj.leu.2402496 . 24297761 .
• Yu Z, Fotouhi-Ardakani N, Wu L, Maoui M, Wang S, Banville D, Shen SH . PTEN associates with the vault particles in HeLa cells . The Journal of Biological Chemistry . 277 . 43 . 40247–40252 . October 2002 . 12177006 . 10.1074/jbc.M207608200 . free .

Notes and References

1. Scheffer GL, Wijngaard PL, Flens MJ, Izquierdo MA, Slovak ML, Pinedo HM, Meijer CJ, Clevers HC, Scheper RJ . The drug resistance-related protein LRP is the human major vault protein . Nature Medicine . 1 . 6 . 578–582 . June 1995 . 7585126 . 10.1038/nm0695-578 . free . 29771830 . 20.500.11755/c49e6086-ede3-4b91-ac6e-4ab9158c6cac .
2. Berger W, Steiner E, Grusch M, Elbling L, Micksche M . Vaults and the major vault protein: novel roles in signal pathway regulation and immunity . Cellular and Molecular Life Sciences . 66 . 1 . 43–61 . January 2009 . 18759128 . 11131553 . 10.1007/s00018-008-8364-z .
3. Web site: Entrez Gene: MVP major vault protein.
4. Kong LB, Siva AC, Rome LH, Stewart PL . Structure of the vault, a ubiquitous celular component . Structure . 7 . 4 . 371–379 . April 1999 . 10196123 . 10.1016/s0969-2126(99)80050-1 . free .
5. Abbondanza C, Rossi V, Roscigno A, Gallo L, Belsito A, Piluso G, Medici N, Nigro V, Molinari AM, Moncharmont B, Puca GA . Interaction of vault particles with estrogen receptor in the MCF-7 breast cancer cell . The Journal of Cell Biology . 141 . 6 . 1301–1310 . June 1998 . 9628887 . 2132791 . 10.1083/jcb.141.6.1301 .
6. Yu Z, Fotouhi-Ardakani N, Wu L, Maoui M, Wang S, Banville D, Shen SH . PTEN associates with the vault particles in HeLa cells . The Journal of Biological Chemistry . 277 . 43 . 40247–40252 . October 2002 . 12177006 . 10.1074/jbc.M207608200 . free .
7. van Zon A, Mossink MH, Schoester M, Scheffer GL, Scheper RJ, Sonneveld P, Wiemer EA . Structural domains of vault proteins: a role for the coiled coil domain in vault assembly . Biochemical and Biophysical Research Communications . 291 . 3 . 535–541 . March 2002 . 11855821 . 10.1006/bbrc.2002.6472 .
8. Kickhoefer VA, Siva AC, Kedersha NL, Inman EM, Ruland C, Streuli M, Rome LH . The 193-kD vault protein, VPARP, is a novel poly(ADP-ribose) polymerase . The Journal of Cell Biology . 146 . 5 . 917–928 . September 1999 . 10477748 . 2169495 . 10.1083/jcb.146.5.917 .