Affinage

MVP

Major vault protein · UniProt Q14764

Length
893 aa
Mass
99.3 kDa
Annotated
2026-06-10
100 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 10/10 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MVP (major vault protein) is the dominant structural subunit of barrel-shaped vault ribonucleoprotein particles, with 48 copies forming each half-vault and all N-termini interacting non-covalently at the vault midsection; co-expression with VPARP or TEP1 recruits these partners into the assembled particle (PMID:15504404). The N-terminal repeat domains R1-R2 mediate half-vault association, and these contacts are disrupted reversibly at acidic pH, providing a pH-gated dissociation mechanism resolved at atomic resolution (PMID:19779459). MVP alone is sufficient to self-assemble vault-shaped particles, and interaction with VPARP is independent of VPARP polymerase activity (PMID:15567158). Beyond its structural role, MVP functions as a multipurpose protein-protein interaction scaffold that tunes signaling: it binds YPEL4 and ZNF540 to modulate MAPK/ERK–Elk-1 transcriptional output (PMID:20555386, PMID:16815308), and its stabilization (e.g., by transglutaminase TG2) drives MAPK/ERK1/2-dependent EMT and metastasis (PMID:41238097). MVP regulates intracellular trafficking, mediating nuclear import of cargoes including PTPN18 with importin β2 to suppress TGF-β/EMT signaling (PMID:35982039), and is itself a cargo of the import receptor KPNA7 (PMID:27664836). MVP controls protein stability of signaling effectors, binding β-TrCP to protect PD-L1 from proteasomal degradation (PMID:40983342) and shaping ferroptosis through interactions with IRF1 that redirect transcription of NOX4, YAP1, and FSP1 (PMID:39143889, PMID:41782382). In bone and immune contexts, MVP restrains calcineurin–NFATc1 osteoclastogenesis (PMID:34158848), couples to Fas to promote osteoclast apoptosis (PMID:37704623), and promotes JAK-STAT-driven M2 macrophage polarization (PMID:37267856, PMID:41961488). MVP also directs selective sorting of miR-193a into exosomes, with loss causing intracellular miR-193a accumulation and Caprin1-dependent cell-cycle arrest (PMID:28211508). MVP activity is regulated by phosphorylation read by 14-3-3ε at Thr52/Ser864 (PMID:23590642) and by succinylation reversed by SIRT7 (PMID:40586636). Notably, genetic knockout established that MVP is not required for classical ABC-transporter–mediated multidrug resistance (PMID:12499273), although it can facilitate nuclear chemotherapeutic export downstream of mechanosensitive Notch signaling (PMID:40333760).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2004 High

    Established the quaternary architecture of the vault and showed MVP is the self-sufficient scaffold that recruits accessory proteins, defining the particle's building principle.

    Evidence CryoEM single-particle reconstruction of recombinant and tissue vaults with VPARP/TEP1 co-expression and difference mapping

    PMID:15504404

    Open questions at the time
    • Did not resolve atomic contacts of half-vault association
    • Functional consequence of VPARP/TEP1 recruitment not addressed
  2. 2005 High

    Demonstrated MVP alone assembles vault-shaped particles and that VPARP incorporation does not require its polymerase activity, separating structural assembly from enzymatic function.

    Evidence E. coli expression reconstitution, pulse-chase immunoprecipitation, and co-sedimentation

    PMID:15567158

    Open questions at the time
    • Slow MVP incorporation kinetics mechanism unexplained
    • Assembly chaperones not identified
  3. 2009 High

    Localized the half-vault association interface to N-terminal repeats R1-R2 and defined a reversible pH-dependent dissociation mechanism, providing a structural basis for vault opening/cargo release.

    Evidence 2.1 Å crystal structure of R1-R7 plus 8 Å vault particle EM

    PMID:19779459

    Open questions at the time
    • Physiological trigger for in vivo dissociation unknown
    • Cargo loading/release coupling to pH change not shown
  4. 2004 Medium

    Defined the transcriptional control of MVP via Sp1/Sp3 GC-box occupancy and LRP130/invMED1, and showed chromatin remodeling (HDAC inhibition) rather than gene amplification drives MVP upregulation in MDR cells.

    Evidence EMSA, ChIP, promoter mutagenesis, dominant-negative Sp1, siRNA, copy-number analysis, HDAC inhibitor treatment

    PMID:15047174 PMID:15093136 PMID:15272088

    Open questions at the time
    • Causal link between MVP induction and drug resistance not established
    • Upstream signals coordinating these factors unclear
  5. 2005 High

    Identified YB-1 as a sequence-specific activator of basal and chemotherapy-inducible MVP transcription, linking stress-responsive transcription factors to MVP expression.

    Evidence EMSA, ChIP, promoter-reporter deletions, YB-1 overexpression/transduction

    PMID:15750632

    Open questions at the time
    • Functional outcome of 5-FU-induced MVP on drug response not tested
    • Signaling that activates YB-1 binding undefined
  6. 2002 High

    Resolved whether MVP confers classical multidrug resistance: genetic knockout showed normal drug sensitivity and unchanged ABC-transporter activity, excluding MVP as a primary MDR effector.

    Evidence MVP knockout mice, cytotoxicity assays in ES/bone marrow cells, ABC-transporter activity assays, in vivo doxorubicin

    PMID:12499273

    Open questions at the time
    • Context-specific drug handling roles not excluded
    • Compensatory mechanisms in KO not characterized
  7. 2010 Medium

    Recast MVP as a signaling scaffold by showing it binds YPEL4 and ZNF540 to modulate MAPK/ERK–Elk-1/SRE transcriptional activity, beyond a purely structural role.

    Evidence Yeast/mammalian two-hybrid, GST pull-down, co-IP, immunocytochemistry, SRE/ELK-1 reporter assays, siRNA

    PMID:16815308 PMID:20555386

    Open questions at the time
    • Whether scaffolding occurs on intact vaults or free MVP unclear
    • Endogenous physiological relevance not established in vivo
  8. 2013 Medium

    Showed MVP function is regulated by phosphorylation, with 14-3-3ε binding phospho-Thr52/Ser864 to inhibit drug-resistant activity and enhance DNA damage response.

    Evidence LC-MS/MS, co-IP, phosphosite mapping, bleomycin treatment, drug resistance assays

    PMID:23590642

    Open questions at the time
    • Upstream kinase not identified
    • Mechanism linking 14-3-3ε binding to DNA damage response undefined
  9. 2017 High

    Established a non-structural trafficking role: MVP selectively sorts miR-193a into exosomes, and its loss traps the miRNA intracellularly to impose Caprin1-dependent cell-cycle arrest.

    Evidence MVP knockout, exosomal miRNA profiling, cell-cycle analysis, Caprin1/Ccnd2/c-Myc target validation

    PMID:28211508

    Open questions at the time
    • Selectivity determinant for miR-193a sorting unknown
    • Whether vault assembly is required for sorting unaddressed
  10. 2018 Medium

    Extended MVP scaffolding to immune signaling and oncogenic MEK activation, binding TBK1 to drive its lysosomal degradation (zebrafish) and bridging B7-H3 to B-RAF/MEK.

    Evidence Co-IP, mass spectrometry, siRNA, IFN reporter and viral infection assays, MEK pathway analysis

    PMID:30082909 PMID:30530482

    Open questions at the time
    • TBK1 degradation finding is in zebrafish ortholog
    • Direct vs indirect B7-H3–MVP binding not fully resolved
  11. 2022 Medium

    Defined MVP as a nuclear transport mediator, importing PTPN18 with importin β2 to dephosphorylate ETS1 and suppress TGF-β/EMT, and being itself a KPNA7 cargo required for cancer growth.

    Evidence Co-IP, subcellular fractionation, overexpression/knockdown, affinity chromatography, cell growth assays

    PMID:27664836 PMID:35982039

    Open questions at the time
    • Generality of MVP as an import adaptor for other cargoes unknown
    • Role of vault particle vs free MVP in transport unclear
  12. 2021 High

    Revealed MVP's physiological role in bone homeostasis, restraining calcineurin–NFATc1 osteoclastogenesis and later coupling to Fas to drive osteoclast apoptosis, with knockout causing osteoporosis.

    Evidence Total-body and monocyte-specific knockout mice, micro-CT, histomorphometry, FK506 rescue, AAV re-expression, co-IP

    PMID:34158848 PMID:37704623

    Open questions at the time
    • Molecular link between MVP and calcineurin regulation not fully defined
    • Whether MVP-Fas acts directly or via adaptors unresolved
  13. 2023 Medium

    Connected MVP to macrophage fate, promoting JAK2-STAT6-driven M2 polarization important for fracture repair and corneal nerve regeneration.

    Evidence Myeloid-specific knockout mice, fracture and nerve regeneration models, macrophage polarization assays, AAV rescue, MG53-MVP K63-ubiquitination assays

    PMID:37267856 PMID:41961488

    Open questions at the time
    • Direct MVP–STAT6 mechanistic coupling incompletely defined
    • Relationship of K63 ubiquitination site to function partly correlative
  14. 2025 High

    Demonstrated MVP controls effector protein stability, binding β-TrCP to stabilize PD-L1 and being itself stabilized by TG2 transamidase activity to drive ERK-dependent EMT.

    Evidence Co-IP, cycloheximide-chase, ubiquitination assays, site-directed mutagenesis/truncations, ChIP-seq, TG2 inhibitor NC9, organoids, xenografts

    PMID:40983342 PMID:41238097

    Open questions at the time
    • How MVP blocks β-TrCP substrate engagement structurally unclear
    • Crosstalk between MVP-stabilizing PTMs not integrated
  15. 2025 Medium

    Established MVP as a node in ferroptosis regulation through RNA binding and transcription-factor sequestration, with PGAM5 dephosphorylation enabling LCN2 mRNA stabilization and IRF1 interactions reprogramming NOX4/YAP1/FSP1 transcription.

    Evidence Phosphatase and RNA-protein binding assays, ferroptosis/lipid peroxidation assays, ChIP, co-IP, ubiquitination assays, tenapanor inhibition, in vivo models

    PMID:39143889 PMID:40262414 PMID:41782382

    Open questions at the time
    • Context-dependent pro- vs anti-ferroptotic roles not reconciled
    • RNA-binding specificity determinants on MVP undefined
  16. 2025 Medium

    Clarified MVP's relationship to drug handling beyond classical MDR, showing mechanosensitive Notch signaling upregulates MVP to facilitate nuclear chemotherapeutic export, and that succinylation reversed by SIRT7 regulates MVP-driven JAK2/STAT3 oncogenic signaling.

    Evidence MVP knockdown, Notch/contractility manipulation, nuclear drug export assays, succinylation/SIRT7 assays, JAK2/STAT3 analysis, xenografts

    PMID:40333760 PMID:40586636

    Open questions at the time
    • Physical mechanism of nuclear drug export by MVP undefined
    • How succinylation alters MVP stability/interactions mechanistically unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MVP toggles between an assembled vault particle and a diffuse signaling/transport/RNA-binding scaffold, and which functions require intact vaults versus free MVP, remains the central unresolved question.
  • No study directly tests vault-assembly dependence of signaling/transport roles
  • Unifying regulatory logic across PTMs and partners not established
  • Structural basis of cargo/partner selectivity unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0005198 structural molecule activity 3 GO:0098772 molecular function regulator activity 3 GO:0003723 RNA binding 2
Localization
GO:0005829 cytosol 3 GO:0005634 nucleus 2 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-168256 Immune System 4 R-HSA-5357801 Programmed Cell Death 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-8953854 Metabolism of RNA 2 R-HSA-9609507 Protein localization 2
Partners
14-3-3ΕB7-H3BTRCIRF1TBK1TEP1VPARPYPEL4
Complex memberships
vault ribonucleoprotein particle

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 Cryoelectron microscopy and single-particle image reconstruction of recombinant and tissue-derived vaults revealed that 48 copies of MVP form each half-vault (96 total), with all MVP N-termini interacting non-covalently at the vault midsection. Co-expression of MVP with VPARP or TEP1 results in their co-assembly into vaults. VPARP was localized by cryoEM difference mapping to three density bands lining the inner surface of the vault. Cryoelectron microscopy, single-particle image reconstruction, recombinant co-expression in insect cells Journal of molecular biology High 15504404
2009 Crystal structure of the seven N-terminal repeat domains (R1-R7) of MVP at 2.1 Å resolution, together with 8 Å vault particle structure, revealed that the interactions governing vault half-association are mediated by the N-terminal domains R1-R2, and that vault halves dissociate reversibly at acidic pH through disruption of these interactions. X-ray crystallography (2.1 Å structure of R1-R7), electron microscopy (8 Å vault particle structure) The EMBO journal High 19779459
2005 Newly synthesized MVP requires more than 4 hours to be incorporated into vault particles, whereas VPARP is completely incorporated within 1.5 hours. Once incorporated, both MVP and VPARP are very stable. Expression of MVP alone in E. coli produces particles with vault morphology, and the C-terminal region of VPARP lacking polyADP-ribose polymerase activity co-sediments with MVP self-assembled vault-like particles, indicating VPARP polymerase activity is not required for interaction with MVP. Immunoprecipitation pulse-chase assay, E. coli expression reconstitution, co-sedimentation assay Biochemical and biophysical research communications High 15567158
2005 YB-1 (Y-box binding protein-1) directly binds the Y-box element in the MVP gene promoter and controls basal and 5-fluorouracil-induced MVP expression. 5-FU amplified YB-1 binding activity to the Y-box in a time-dependent manner. Stable YB-1 overexpression enhanced binding and increased basal and 5-FU-inducible MVP promoter-driven reporter expression. YB-1 cDNA transduction led to increased endogenous MVP protein expression. Electrophoretic mobility shift assay (EMSA), ChIP, MVP promoter-reporter deletion mutants, YB-1 stable overexpression, YB-1 cDNA transduction Oncogene High 15750632
2004 SP-family transcription factors (Sp1, Sp3) bind a conserved proximal GC-box element essential for basal human MVP promoter transactivation. Dominant-negative Sp1 and mithramycin A attenuated MVP promoter activity. HDAC inhibitors (butyrate, trichostatin A) potently stimulated MVP expression by shifting Sp1 to Sp3 occupancy at this GC-box, demonstrated by ChIP assays. EMSA, ChIP, MVP promoter deletion/mutation analysis, dominant-negative Sp1, mithramycin A treatment, HDAC inhibitor treatment Biochemical and biophysical research communications High 15047174
2004 The LRP130 protein binds the invMED1 cis-element located at -148/-143 in the MVP gene promoter and is involved in transcriptional activation of MVP. SiRNA knockdown of LRP130 and transcriptional decoys targeting invMED1 reduced endogenous MVP gene activity in two unrelated human cancer cell lines. siRNA knockdown, transcriptional decoy competition, promoter-reporter assays Nucleic acids research Medium 15272088
2004 Drug resistance in multi-drug resistant cancer cell lines is not caused by vault gene amplification. Treatment with HDAC inhibitors (sodium butyrate, trichostatin A) increased MVP mRNA, protein, and promoter activity, suggesting chromatin remodeling regulates MVP upregulation in MDR. Gene copy number analysis, RT-PCR, Western blot, promoter-reporter assays, HDAC inhibitor treatment Biochimica et biophysica acta Medium 15093136
2010 MVP physically interacts with YPEL4 and inhibits YPEL4-mediated activation of Elk-1 in the MAPK signaling pathway. The interaction was confirmed by yeast two-hybrid, mammalian two-hybrid, GST pull-down, co-immunoprecipitation, and immunocytochemistry. Reporter assays showed MVP suppresses YPEL4-driven transcriptional activity through the ERK pathway. Yeast two-hybrid, mammalian two-hybrid, GST pull-down, co-immunoprecipitation, immunocytochemistry, reporter gene assay Biochemistry and cell biology Medium 20555386
2006 MVP interacts with zinc finger protein ZNF540 as identified by yeast two-hybrid screening and confirmed by co-immunoprecipitation. ZNF540 represses SRE and ELK-1 transcriptional activities, and MVP is identified as a MAPK scaffold protein in this pathway. Yeast two-hybrid, co-immunoprecipitation, reporter gene assay (SRE, ELK-1), siRNA knockdown Biochemical and biophysical research communications Medium 16815308
2002 MVP/LRP knockout mice are viable, healthy, and show no obvious abnormalities. MVP-deficient embryonic stem cells and bone marrow cells showed no increased sensitivity to cytostatic agents compared to wild-type cells. ABC-transporter activities (P-glycoprotein, MRP, BCRP) were unaltered upon MVP deletion. MVP knockout mice responded to doxorubicin treatment similarly to wild-type mice. MVP knockout mouse generation, cytotoxicity assays (embryonic stem cells, bone marrow), ABC-transporter activity assays, in vivo doxorubicin treatment Cancer research High 12499273
2017 MVP mediates selective sorting of miR-193a into exosomes. Knockout of MVP leads to miR-193a accumulation in donor cells instead of exosomes, inhibiting tumor progression. Accumulated miR-193a causes G1 cell cycle arrest and represses proliferation by targeting Caprin1, which upregulates Ccnd2 and c-Myc. MVP knockout, exosomal miRNA profiling, cell cycle analysis, target validation (Caprin1, Ccnd2, c-Myc) Nature communications High 28211508
2018 B7-H3 interacts with MVP as identified by immunoprecipitation and mass spectrometry. MVP enhances B-RAF and MEK interaction to activate MEK signaling. B7-H3-induced MEK activation and cancer stem cell enrichment are blocked by MVP depletion. Immunoprecipitation, mass spectrometry, MVP siRNA knockdown, MEK pathway analysis Oncogene Medium 30082909
2013 14-3-3ε binds to MVP in a phosphorylation-dependent manner at both Thr52 and Ser864 of the MVP monomer. This interaction is induced by bleomycin treatment and inhibits the drug-resistant activity of MVP, enhancing the DNA damage response. LC-MS/MS proteomics, co-immunoprecipitation, phosphorylation site identification, functional drug resistance assays Journal of proteome research Medium 23590642
2018 Zebrafish MVP interacts with TBK1 and recruits it from a uniformly distributed cytoplasmic state to an aggregated state, then mediates lysosome-dependent degradation of TBK1. This suppresses IFN production downstream of RIG-I-like receptor signaling. Co-immunoprecipitation, overexpression studies, lysosome inhibitor treatment, IFN reporter assays, viral infection experiments Journal of immunology Medium 30530482
2021 MVP negatively regulates osteoclastogenesis via inhibition of calcineurin-NFATc1 signaling. MVP deficiency enhances calcineurin-NFATc1 signaling and promotes osteoclast differentiation and bone resorption. Calcineurin inhibition with FK506 corrected the enhanced osteoclastogenesis in MVP knockout mice. MVP re-expression in knockout mice rescued calcineurin expression. Total body and monocyte-specific MVP knockout mice, micro-CT, bone histomorphometry, in vitro osteoclast differentiation assays, FK506 treatment, AAV-mediated MVP re-expression Theranostics High 34158848
2023 MVP interacts with death receptor Fas in osteoclasts, and the MVP-Fas signaling cascade positively regulates osteoclast apoptosis. Conditional MVP knockout in monocyte lineage inhibited osteoclast apoptosis in vivo and in vitro, leading to osteoporosis in aging and estrogen-deficient mouse models. Conditional MVP knockout mice (Mvpf/fLyz2-Cre), co-immunoprecipitation (MVP-Fas interaction), in vivo and in vitro apoptosis assays Cell death & disease Medium 37704623
2022 MVP translocates PTPN18 from cytoplasm to nucleus together with importin β2 in breast cancer cells. Nuclear PTPN18 (but not cytoplasmic) dephosphorylates ETS1 and promotes its degradation, suppressing TGF-β signaling and EMT. Co-immunoprecipitation, subcellular fractionation, MVP overexpression/knockdown, PTPN18 localization studies Cell death & disease Medium 35982039
2016 MVP is a cargo protein of the nuclear import receptor KPNA7. KPNA7 silencing hindered MVP transport to the nucleus. MVP knockdown caused marked reduction in pancreatic cancer cell growth. Protein affinity chromatography, co-immunoprecipitation, siRNA-mediated KPNA7 silencing, cell growth assays Biochimica et biophysica acta. Molecular basis of disease Medium 27664836
2025 MVP binds β-TrCP and prevents β-TrCP-mediated proteasomal degradation of PD-L1, thereby stabilizing PD-L1 protein. Histone lactylation transcriptionally upregulates MVP. Site-directed mutagenesis and truncation mutants identified the binding sites of the MVP-β-TrCP complex. Co-immunoprecipitation, cycloheximide-chase analysis, ubiquitination assay, site-directed mutagenesis, truncation mutants, ChIP-seq Journal for immunotherapy of cancer High 40983342
2025 PGAM5 directly dephosphorylates MVP at Ser873, facilitating MVP binding to LCN2 mRNA and maintaining its stability. This attenuates ferroptosis by reducing lipid peroxidation and intracellular Fe²⁺. Tenapanor disrupts the MVP-LCN2 mRNA interaction. ROS-induced STAT3 transcriptionally activates MVP expression in HCC. Phosphatase assay (PGAM5-MVP), RNA-protein binding assay (MVP-LCN2 mRNA), ferroptosis assays, STAT3 ChIP, tenapanor inhibition Drug resistance updates Medium 40262414
2024 MVP binds IRF1 and interferes with IRF1 interaction with the YAP1 promoter, leading to increased NOX4 transcription and enhanced lipid peroxidation. This promotes FGF21-induced ferroptosis in HCC cells. MVP knockdown reduced NOX4 transcription and attenuated FGF21-mediated ferroptosis. Co-immunoprecipitation (MVP-IRF1), ChIP assay (IRF1-YAP1 promoter), MVP knockdown/overexpression, ferroptosis/lipid peroxidation assays, xenograft models Clinical and translational science Medium 39143889
2025 TG2 binds MVP and stabilizes it by inhibiting ubiquitin-proteasomal degradation in a transamidase activity-dependent manner. Accumulation of MVP facilitates MAPK/ERK1/2 signaling activation, inducing EMT and metastasis in basal-like bladder cancer. Co-immunoprecipitation (TG2-MVP), ubiquitination assays, proteasome inhibitor treatment, TG2 catalytic inhibitor NC9, ERK signaling analysis, patient-derived organoids, in vivo xenograft Cancer letters Medium 41238097
2025 MVP undergoes succinylation modification; SIRT7 is the desuccinylase for MVP and promotes MVP protein stability in TSCC cells. Desuccinylated MVP activates JAK2/STAT3 pathway to promote TSCC cell proliferation, migration, and invasion. JAK2 agonist CA1 reversed the effects of MVP silencing. Succinylation assay, SIRT7 co-expression/knockdown, Western blot (MVP stability), JAK2/STAT3 pathway analysis, functional cell assays Cell biology international Medium 40586636
2023 MVP promotes M2 macrophage polarization during fracture repair via the JAK2-STAT6 pathway. Myeloid-specific MVP knockout mice showed impaired transition from pro-inflammatory to anti-inflammatory macrophage phenotype, increased pro-inflammatory cytokines, enhanced osteoclastogenesis, and impaired fracture healing. AAV-Mvp injection rescued fracture repair. Myeloid-specific MVP knockout mice (Mvpf/fLyz2-Cre), in vivo fracture model, macrophage polarization assays, cytokine measurement, JAK2-STAT6 pathway analysis, AAV rescue International immunopharmacology Medium 37267856
2025 Intercellular force activates Notch signaling which upregulates MVP expression, and MVP facilitates export of chemotherapy drugs from nuclei. Inhibition of contractile force, Notch signaling, or MVP each reversed drug export and restored chemosensitivity in vitro and in vivo. MVP knockdown, Notch inhibition, contractility manipulation, nuclear drug export assays, xenograft tumor models Proceedings of the National Academy of Sciences Medium 40333760
2015 MVP-associated Filamin A mutations (G288R, P637Q, H743P) abolish FlnA/PTPN12 (PTP-PEST) interactions. Loss of this interaction impairs activation of PTPN12 substrates Src and p190RhoGAP, affecting focal adhesion signaling and actin cytoskeleton dynamics in the context of mitral valve prolapse pathogenesis. Yeast two-hybrid, pull-down, co-immunoprecipitation, kinase activity assays (Src, p190RhoGAP) Journal of cardiovascular development and disease Low 26594644
2026 MVP sequesters IRF1 from TRAF6, suppressing IRF1 polyubiquitination and nuclear localization during IAV infection. This prevents IRF1 transcriptional repression of the FSP1 promoter, thereby increasing FSP1 expression and plasma membrane recruitment, enabling ferroptosis suppression. Co-immunoprecipitation (MVP-IRF1, IRF1-TRAF6), ubiquitination assay, FSP1 promoter reporter, in vitro and in vivo ferroptosis assays, myristoylation/membrane recruitment assays Advanced science Medium 41782382
2026 MG53 interacts with MVP and promotes K63-linked ubiquitination of MVP at lysine 747, facilitating STAT6 nuclear translocation and transcriptional activation of M2 macrophage genes to promote corneal nerve regeneration. Co-immunoprecipitation (MG53-MVP), K63-ubiquitination assay, STAT6 nuclear translocation assay, genome-wide Membrane Proteome Array screen, in vivo nerve regeneration model Advanced science Medium 41961488

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 MVP-mediated exosomal sorting of miR-193a promotes colon cancer progression. Nature communications 391 28211508
1994 A new subtype of human immunodeficiency virus type 1 (MVP-5180) from Cameroon. Journal of virology 317 8107219
1995 Symptom relief with MVP (mitomycin C, vinblastine and cisplatin) chemotherapy in advanced non-small-cell lung cancer. British journal of cancer 152 7530988
2021 MVP predicts the pathogenicity of missense variants by deep learning. Nature communications 133 33479230
2012 Overcoming drug resistance of MCF-7/ADR cells by altering intracellular distribution of doxorubicin via MVP knockdown with a novel siRNA polyamidoamine-hyaluronic acid complex. Journal of controlled release : official journal of the Controlled Release Society 120 22940126
2002 Teratogenicity of a mutagenised Rift Valley fever virus (MVP 12) in sheep. The Onderstepoort journal of veterinary research 107 12092782
2019 Adipocytes promote breast cancer resistance to chemotherapy, a process amplified by obesity: role of the major vault protein (MVP). Breast cancer research : BCR 105 30654824
2018 Immunoregulatory protein B7-H3 regulates cancer stem cell enrichment and drug resistance through MVP-mediated MEK activation. Oncogene 92 30082909
2002 Disruption of the murine major vault protein (MVP/LRP) gene does not induce hypersensitivity to cytostatics. Cancer research 85 12499273
2004 Cryoelectron microscopy imaging of recombinant and tissue derived vaults: localization of the MVP N termini and VPARP. Journal of molecular biology 75 15504404
2011 Development of imatinib and dasatinib resistance: dynamics of expression of drug transporters ABCB1, ABCC1, ABCG2, MVP, and SLC22A1. Leukemia & lymphoma 59 21663515
2006 A phase III trial of docetaxel/carboplatin versus mitomycin C/ifosfamide/cisplatin (MIC) or mitomycin C/vinblastine/cisplatin (MVP) in patients with advanced non-small-cell lung cancer: a randomised multicentre trial of the British Thoracic Oncology Group (BTOG1). Annals of oncology : official journal of the European Society for Medical Oncology 57 16603599
1999 Increased expression of multidrug resistance related proteins Pgp, MRP1, and LRP/MVP occurs early in colorectal carcinogenesis. Journal of clinical pathology 47 10562814
2005 YB-1 facilitates basal and 5-fluorouracil-inducible expression of the human major vault protein (MVP) gene. Oncogene 45 15750632
2011 MVP and vaults: a role in the radiation response. Radiation oncology (London, England) 40 22040803
2003 Hyperpolarization moves S4 sensors inward to open MVP, a methanococcal voltage-gated potassium channel. Nature neuroscience 39 12640457
2000 Cloning and initial analysis of the human multidrug resistance-related MVP/LRP gene promoter. Biochemical and biophysical research communications 39 11071864
2009 Severe hypoxia induces chemo-resistance in clinical cervical tumors through MVP over-expression. Radiation oncology (London, England) 37 19660100
1983 Phase II trial of mitomycin, vinblastine, and cisplatin (MVP) in non-small cell bronchogenic carcinoma. Cancer treatment reports 35 6684988
1999 Do P-glycoprotein and major vault protein (MVP/LRP) expression correlate with in vitro daunorubicin resistance in acute myeloid leukemia? Leukemia 34 10025900
2010 MVP interacts with YPEL4 and inhibits YPEL4-mediated activities of the ERK signal pathway. Biochemistry and cell biology = Biochimie et biologie cellulaire 33 20555386
2002 Expression of multidrug resistance genes MVP, MDR1, and MRP1 determined sequentially before, during, and after hyperthermic isolated limb perfusion of soft tissue sarcoma and melanoma patients. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 33 12149303
2011 Exogenous or endogenous Toll-like receptor ligands: which is the MVP in tumorigenesis? Cellular and molecular life sciences : CMLS 32 22048194
2004 The palliative benefits of MVP (mitomycin C, vinblastine and cisplatin) chemotherapy in patients with malignant mesothelioma. Annals of oncology : official journal of the European Society for Medical Oncology 32 15319247
2021 Major vault protein (MVP) negatively regulates osteoclastogenesis via calcineurin-NFATc1 pathway inhibition. Theranostics 31 34158848
2022 Major Vault Protein (MVP) Associated With BRAF V600E Mutation Is an Immune Microenvironment-Related Biomarker Promoting the Progression of Papillary Thyroid Cancer via MAPK/ERK and PI3K/AKT Pathways. Frontiers in cell and developmental biology 30 35433709
1996 Mitomycin C plus vindesine plus etoposide (MEV) versus mitomycin C plus vindesine plus cisplatin (MVP) in stage IV non-small-cell lung cancer: A phase III multicentre randomised trial. The "Gruppo Oncologico Centro-Sud-Isole' (G.O.C.S.I.). Annals of oncology : official journal of the European Society for Medical Oncology 30 8922196
2009 The mechanism of vault opening from the high resolution structure of the N-terminal repeats of MVP. The EMBO journal 28 19779459
2004 New invMED1 element cis-activates human multidrug-related MDR1 and MVP genes, involving the LRP130 protein. Nucleic acids research 28 15272088
1998 Cisplatin-vindesine-mitomycin (MVP) vs cisplatin-ifosfamide-vinorelbine (PIN) vs carboplatin-vinorelbine (CaN) in patients with advanced non-small-cell lung cancer (NSCLC): a FONICAP randomized phase II study. Italian Lung Cancer Task Force (FONICAP). British journal of cancer 28 9649160
2006 A novel human zinc finger protein ZNF540 interacts with MVP and inhibits transcriptional activities of the ERK signal pathway. Biochemical and biophysical research communications 27 16815308
2005 Expression and proteasomal degradation of the major vault protein (MVP) in mammalian oocytes and zygotes. Reproduction (Cambridge, England) 27 15749954
2022 Nuclear import of PTPN18 inhibits breast cancer metastasis mediated by MVP and importin β2. Cell death & disease 25 35982039
2005 Characterization of MVP and VPARP assembly into vault ribonucleoprotein complexes. Biochemical and biophysical research communications 24 15567158
2004 SP-transcription factors are involved in basal MVP promoter activity and its stimulation by HDAC inhibitors. Biochemical and biophysical research communications 24 15047174
2018 Zebrafish MVP Recruits and Degrades TBK1 To Suppress IFN Production. Journal of immunology (Baltimore, Md. : 1950) 23 30530482
2015 MVP-Associated Filamin A Mutations Affect FlnA-PTPN12 (PTP-PEST) Interactions. Journal of cardiovascular development and disease 23 26594644
2011 BCL-2, in combination with MVP and IGF-1R expression, improves prediction of clinical outcome in complete response cervical carcinoma patients treated by radiochemotherapy. Gynecologic oncology 23 21708403
1999 The major vault protein (MVP), a new multidrug resistance associated protein, is frequently expressed in multiple myeloma. Leukemia & lymphoma 23 10439368
2003 Unimpaired dendritic cell functions in MVP/LRP knockout mice. Immunology 21 12941141
2008 MVP expression is related to IGF1-R in cervical carcinoma patients treated by radiochemotherapy. Gynecologic oncology 19 18599112
1991 Abnormal guanine nucleotide regulatory protein in MVP dysautonomia: evidence from reconstitution of Gs. The Journal of clinical endocrinology and metabolism 17 1900864
2020 Y-box binding protein 1 (YB-1) promotes gefitinib resistance in lung adenocarcinoma cells by activating AKT signaling and epithelial-mesenchymal transition through targeting major vault protein (MVP). Cellular oncology (Dordrecht, Netherlands) 16 32894437
2025 MVP-LCN2 axis triggers evasion of ferroptosis to drive hepatocarcinogenesis and sorafenib resistance. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy 15 40262414
2021 Chromatin Accessibility of Human Mitral Valves and Functional Assessment of MVP Risk Loci. Circulation research 15 33508947
2021 MVP Expression Facilitates Tumor Cell Proliferation and Migration Supporting the Metastasis of Colorectal Cancer Cells. International journal of molecular sciences 15 34829999
2018 The WT1/MVP-Mediated Stabilization on mTOR/AKT Axis Enhances the Effects of Cisplatin in Non-small Cell Lung Cancer by a Reformulated Yu Ping Feng San Herbal Preparation. Frontiers in pharmacology 15 30131696
2013 Major vault protein (MVP) gene polymorphisms and drug resistance in mesial temporal lobe epilepsy with hippocampal sclerosis. Gene 15 23751308
2023 Major vault protein (MVP) suppresses aging- and estrogen deficiency-related bone loss through Fas-mediated apoptosis in osteoclasts. Cell death & disease 14 37704623
2021 Novel cancer stem cell marker MVP enhances temozolomide-resistance in glioblastoma. Translational oncology 14 34742152
2016 Search for KPNA7 cargo proteins in human cells reveals MVP and ZNF414 as novel regulators of cancer cell growth. Biochimica et biophysica acta. Molecular basis of disease 14 27664836
2013 14-3-3ε boosts bleomycin-induced DNA damage response by inhibiting the drug-resistant activity of MVP. Journal of proteome research 14 23590642
2012 MVP expression in the prediction of clinical outcome of locally advanced oral squamous cell carcinoma patients treated with radiotherapy. Radiation oncology (London, England) 14 22931894
2015 Pleiotropic effect of chromosome 5A and the mvp mutation on the metabolite profile during cold acclimation and the vegetative/generative transition in wheat. BMC plant biology 13 25848884
2016 Association of single nucleotide polymorphisms in the MVP gene with platinum resistance and survival in patients with epithelial ovarian cancer. Oncology letters 12 27073578
2023 Long-term Outcomes in Primary CNS Lymphoma After R-MVP and High-Dose Chemotherapy With Autologous Hematopoietic Stem Cell Transplant. Neurology 11 37344228
2017 vPARP Adjusts MVP Expression in Drug-resistant Cell Lines in Conjunction with MDR Proteins. Anticancer research 11 28551640
2017 Expression of the Major Vault Protein (MVP) and Cellular Vault Particles in Fish. Anatomical record (Hoboken, N.J. : 2007) 11 28710803
2001 Detection of the Mr 110,000 lung resistance-related protein LRP/MVP with monoclonal antibodies. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 11 11668191
1998 A pilot study of MVP (mitomycin-C, vinblastine and cisplatin) chemotherapy in small-cell lung cancer. British journal of cancer 10 9667676
1995 Effectiveness and toxicity of preoperative therapy in stage IIIA non-small cell lung cancer including the Memorial Sloan-Kettering experience with induction MVP in patients with bulky mediastinal lymph node metastases (Clinical N2). Lung cancer (Amsterdam, Netherlands) 10 7551934
2025 Lactylation-driven MVP upregulation boosts immunotherapy resistance by inhibiting PD-L1 degradation in hepatocellular carcinoma. Journal for immunotherapy of cancer 9 40983342
2024 MVP enhances FGF21-induced ferroptosis in hepatocellular carcinoma by increasing lipid peroxidation through regulation of NOX4. Clinical and translational science 9 39143889
2014 Biochemical and structural analysis of the hyperpolarization-activated K(+) channel MVP. Biochemistry 9 24490868
2004 Analysis of MVP and VPARP promoters indicates a role for chromatin remodeling in the regulation of MVP. Biochimica et biophysica acta 9 15093136
2023 PD-L1 expression predicts efficacy in the phase II SPiReL trial with MVP-S, pembrolizumab, and low-dose CPA in R/R DLBCL. European journal of haematology 8 37157906
2022 Analysis of Multiple Drug Resistance Mechanism in Different Types of Soft Tissue Sarcomas: Assessment of the Expression of ABC-Transporters, MVP, YB-1, and Analysis of Their Correlation with Chemosensitivity of Cancer Cells. International journal of molecular sciences 7 35328603
1991 Influence of pretreatment clinical characteristics on the response rate to mitomycin/vindesine/cisplatin (MVP) in unresectable non-small cell lung cancer. ATTIT (Association pour le Traitement des Tumeurs Intra-Thoraciques). European journal of cancer (Oxford, England : 1990) 7 1659842
2018 MVP immunohistochemistry is a useful adjunct in distinguishing leiomyosarcoma from leiomyoma and leiomyoma with bizarre nuclei. Human pathology 6 29307622
2018 Inhibition of RM-1 prostate carcinoma and eliciting robust immune responses in the mouse model by using VEGF-M2-GnRH3-hinge-MVP vaccine. Genes and immunity 6 29362508
2016 Connection between Proliferation Rate and Temozolomide Sensitivity of Primary Glioblastoma Cell Culture and Expression of YB-1 and LRP/MVP. Biochemistry. Biokhimiia 6 27301292
1997 Advanced non-small cell lung cancer chemotherapy: a randomized trial of two active regimens (MVP and PE). Cancer letters 6 9570378
1994 Comparison of two chemotherapeutic regimens--mitomycin + vindesine + cisplatin (MVP) vs. mitomycin + ifosfamide + cisplatin (MIP)--in advanced non-small-cell lung cancer. ONCOPAZ Cooperative Group. Annals of oncology : official journal of the European Society for Medical Oncology 6 8075028
2025 Intercellular contractile force attenuates chemosensitivity through Notch-MVP-mediated nuclear drug export. Proceedings of the National Academy of Sciences of the United States of America 5 40333760
2023 Macrophage MVP regulates fracture repair by promoting M2 polarization via JAK2-STAT6 pathway. International immunopharmacology 5 37267856
2022 Role of upfront autologous stem cell transplantation in patients newly diagnosed with primary CNS lymphoma treated with R-MVP: real-world data from a retrospective single-center analysis. Bone marrow transplantation 5 35173287
2002 Major vault protein/lung resistance-related protein (MVP/LRP) expression in nervous system tumors. Brain tumor pathology 5 12622134
1996 Is the MVP regimen less active than previously described? Results of a phase II study in advanced non-small cell lung cancer. Acta oncologica (Stockholm, Sweden) 5 8695157
2015 Absence of association between major vault protein (MVP) gene polymorphisms and drug resistance in Chinese Han patients with partial epilepsy. Journal of the neurological sciences 4 26476776
2024 Design and pilot results from the Million Veteran Program Return Of Actionable Results (MVP-ROAR) Study. American heart journal 3 38762090
2024 MiR-140-3p Improves Sensitivity to Docetaxel by Suppressing PD-L1/ABCG2/MVP Expression in Lung Adenocarcinoma. Anticancer research 3 39348965
2025 DS-MVP: identifying disease-specific pathogenicity of missense variants by pre-training representation. Briefings in bioinformatics 2 40127180
2024 Proteomic Analysis of Microsomal Proteins Reveals That MVP Is Crucial for the Secretion of GDF-15, Which in Turn Promotes the Neuroendocrine Differentiation of PCa Cells. Journal of proteome research 2 39472282
1993 Adjuvant chemotherapy for invasive urothelial cancer: experience with a methotrexate, vincristine, cisplatin, cyclophosphamide, adriamycin and bleomycin (MVP-CAB) regimen: a preliminary report. Japanese journal of clinical oncology 2 7693990
1992 [Adjuvant chemotherapy with MVP-CAB (methotrexate, vincristine, cisplatinum, cyclophosphamide, adriamycin and bleomycin) for epithelial tumors of the upper urinary tract]. Nihon Hinyokika Gakkai zasshi. The japanese journal of urology 2 1279258
2025 Prevalence and disease risks for male and female sex chromosome trisomies: a registry-based phenome-wide association study in 1.5 million participants of MVP, FinnGen, and UK Biobank. medRxiv : the preprint server for health sciences 1 39974076
2025 SIRT7-Mediated MVP Desuccinylation Facilitates Tongue Squamous Cell Carcinoma Progression by Activating JAK2/STAT3 Pathway. Cell biology international 1 40586636
2025 Phenome-wide association study of male and female sex chromosome trisomies in 1.5 million participants of MVP, FinnGen, and UK Biobank. American journal of human genetics 1 40840450
2025 VIRUS-MVP: a framework for comprehensive surveillance of viral mutations and their functional impacts. NAR genomics and bioinformatics 1 41064595
2025 Transglutaminase 2 facilitates metastasis of basal-like bladder cancer by sustaining MVP-mediated MAPK/ERK1/2 signaling activation. Cancer letters 1 41238097
2012 Does reducing unnecessary right ventricular pacing improve sympathetic activity and innervation of heart in sinus node disease patients? MVP and SafeR study. International heart journal 1 23258135
1990 Preliminary experience with mitomycin, vinblastine and cisplatin (MVP) combination chemotherapy in the treatment of advanced non-small cell lung cancer at University Hospital, Kuala Lumpur. Singapore medical journal 1 2168091
2026 MVP Inhibits Influenza A Virus-Induced Ferroptosis by Targeting IRF1 and Increasing FSP1 Activity. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 41782382
2026 MG53 Coordinates Macrophage Polarization and Neuroimmune Coupling to Promote Corneal Nerve Regeneration via the MPEG1-MVP-STAT6 Axis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 41961488
2025 Investigation into the sensitivity of adipocytes mediated by the major vault protein (MVP) to chemotherapy for triple-negative breast cancer. Translational cancer research 0 40950669
2004 [Prospective randomized study of HMVP, MVP, and HVP regimens in treatment of advanced non-small cell lung cancer]. Ai zheng = Aizheng = Chinese journal of cancer 0 15087034
2004 [Efficacy of MVP chemotherapy combined with concurrent radiotherapy for advanced non-small cell lung cancer]. Zhongguo fei ai za zhi = Chinese journal of lung cancer 0 21251408
2003 [Establishment of human multidrug-resistant lung carcinoma cell line (D6/MVP)]. Zhonghua zhong liu za zhi [Chinese journal of oncology] 0 12795837
2002 [Comparison of NP and MVP regimen in treatment of advanced non-small cell lung cancer]. Ai zheng = Aizheng = Chinese journal of cancer 0 12520749
1988 Understanding mitral valve prolapse (MVP). Herz 0 3049286

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