Cloning and Initial Analysis of the Human Multidrug Resistance-Related MVP/LRP Gene Promoter

Lange, Christian; Walther, Wolfgang; Schwabe, Holger; Stein, Ulrike

doi:10.1006/bbrc.2000.3782

Cited by 40 publications

(37 citation statements)

References 33 publications

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“…26 In this study, we observed that the levels of MVP protein and mRNA were downregulated only in young HDFs, but not in senescent HDFs, treated with apoptosis-inducing agents such as H 2 O 2 , staurosporine and thapsigargin (Figure 2), suggesting age dependency of MVP response. Human MVP gene contains transcription factor-binding sites for p53, STAT1, Sp1 and MyoD, 32,33 and transcription factors including STAT1, YB-1 and Sp-1 are involved in the regulation of MVP in different cell types. 14,32,34 Interestingly, we observed that the basal and phosphorylation status of p53 are either increased or decreased in specific agonist-induced apoptosis of young HDFs, but the status of other transcription factors for MVP such as STAT1, Sp1 and MyoD did not change (data not shown).…”

Section: Discussionmentioning

confidence: 99%

On the role of major vault protein in the resistance of senescent human diploid fibroblasts to apoptosis

Ryu

et al. 2008

Cell Death Differ

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Major vault protein (MVP), the main component of vault complex, is overexpressed in many multidrug-resistant cancer cell lines, suggesting a possible role for MVP in cell signaling and survival. In this study, we have found that MVP is markedly increased in senescent human diploid fibroblasts (HDFs) as well as in aged organs. We examined whether MVP expression might be affected by apoptotic stress in an aging-dependent manner. We treated young and senescent HDFs with apoptosis-inducing agents such as H 2 O 2 , staurosporine and thapsigargin, and monitored MVP expression. We found that MVP expression is markedly reduced in young HDFs but not in senescent HDFs, in response to apoptotic stresses. Downregulation of MVP increased the sensitivity of senescent HDFs to apoptosis. Also, the level of antiapoptotic B-cell lymphoma protein-2 (Bcl-2) was significantly reduced and the accumulation of c-Jun increased in MVP knocked-down senescent HDFs. Moreover, treatment of MVP knocked-down senescent HDFs with SP600125, a specific c-Jun NH (2) Vaults are large ribonucleoprotein particles found in a great portion of eukaryotic cells. The vault particle is a multimeric structure composed of three proteins -the major vault protein (MVP), two minor vault proteins, vault poly (ADP-ribose) polymerase (VPARP) and telomerase-associated protein-1 (TP-1), and four small untranslated vault RNAs (vRNAs). 1 MVP is the main component of the vault complex accounting for 75% of the total particle mass. 2 The vault particle has been so named because it has a barrel-shaped structure, reminiscent of the vaulted ceilings in cathedrals. 3 The interaction of MVP by its coiled coil domain is involved in the formation of the basic vault complex. 4 MVP expression is upregulated in cancers such as melanoma, 5 colon cancer 6 and gliomas 7 during acquisition of multidrug resistance 8,9 and during differentiation of dendritic cells. 10 MVP expression has also been shown to be induced by histone deacetylase inhibitors such as sodium butyrate, 11 phorbol 12-myristate 13-acetate (PMA) and cytarabine 12 as well as by cytotoxic drugs. 12-14 MVP/vaults have been proposed to be important in intracellular transport, 15-17 innate immunity 18 and virus infection. 19 Several studies demonstrated that MVP is important in cell signaling [20][21][22] and in cell survival. 10,20,23 For example, serumdeprived MVP-deficient mouse embryonic fibroblasts (MEFs) exhibit significantly increased cell death when compared with wild-type MEFs. 20 Therefore, the role of MVP as a scaffolding protein for signaling proteins, especially for cell survival, has received more attention than as a transport vehicle. However, the exact role of MVP in cell survival is not well understood. In this study, we found that apoptotic resistance of senescent human diploid fibroblasts (HDFs) correlates with the increased content of MVP in the senescent cells. This is the first report implicating MVP in apoptosis resistance of senescent HDFs. ResultsIncreased expression of MVP in aged cells and organs...

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Section: Discussionmentioning

confidence: 99%

On the role of major vault protein in the resistance of senescent human diploid fibroblasts to apoptosis

Ryu

et al. 2008

Cell Death Differ

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“…We previously identified several putative consensus sequence motifs for transcription factors within the MVP promoter (Lange et al, 2000), including a Y-box motif at position À279 to À275 upstream of the transcriptional initiation site. To investigate the role of YB-1 in MVP gene regulation, we examined whether YB-1 is able to bind to the Y-box motif of the MVP promoter.…”

Section: Yb-1 Mediates Transcriptional Regulation Of Mvp U Stein Et Almentioning

confidence: 99%

“…For a more detailed analysis of the transcriptional regulation of the human MVP promoter by YB-1, pCAT-MVP promoter deletion mutants were generated using our previously isolated 1881 bp long MVP promoter fragment (MVP1.9) (Lange et al, 2000). Schematic drawings of the reporter constructs pCAT-MVP1.9, pCAT-MVP0.7, pCAT-MVP0.3, and pCAT-MVP0.13 are shown in Figure 4a.…”

Section: Yb-1 Mediates Transcriptional Regulation Of Mvp U Stein Et Almentioning

confidence: 99%

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YB-1 facilitates basal and 5-fluorouracil-inducible expression of the human major vault protein (MVP) gene

et al. 2005

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Vaults have been suggested to play a direct role in multidrug resistance (MDR) to anticancer drugs. The human major vault protein (MVP) also known as lung resistance-related protein (LRP) represents the predominant component of vaults that may be involved in the defense against xenobiotics. Here, we demonstrate that besides MDR-related cytostatics, also the non-MDRrelated drug 5-fluorouracil (5-FU) was able to induce MVP mRNA and protein expression. Treatment with 5-FU amplified the binding activity and interaction of the transcription factor Y-box binding protein-1 (YB-1) with the Y-box of the human MVP gene promoter in a timedependent manner. 5-FU also induced reporter expressions driven by a panel of newly generated MVP promoter deletion mutants. Interestingly, stably YB-1 overexpressing cell clones showed enhanced binding of YB-1 to the Y-box motif, associated with enhanced basal as well as 5-FU-inducible MVP promoter-driven reporter expressions. Moreover, transduction of YB-1 cDNA led to increased expression of endogenous MVP protein. Under physiological conditions, we observed a strong coexpression of MVP and YB-1 in human colon carcinoma specimen. In summary, our data demonstrate a direct involvement of YB-1 in controlling basal and 5-FUinduced MVP promoter activity. Therefore, YB-1 is directly linked to MVP-mediated drug resistance.

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“…Recently, regulatory roles of chromatin remodeling (Emre et al, 2004) as well as alternative splicing (Holzmann et al, 2001) have been suggested. An initial analysis of the human MVP gene revealed a TATA-less promoter, which also lacks other core-promoter elements but harbors several putative transcription factor binding sites, including an inverted CCAAT box, a p53-binding site, and a GC box element (Lange et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

The major vault protein is responsive to and interferes with interferon-γ-mediated STAT1 signals

Steiner

Holzmann

Pirker

et al. 2006

Journal of Cell Science

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Cloning and Initial Analysis of the Human Multidrug Resistance-Related MVP/LRP Gene Promoter

Cited by 40 publications

References 33 publications

On the role of major vault protein in the resistance of senescent human diploid fibroblasts to apoptosis

On the role of major vault protein in the resistance of senescent human diploid fibroblasts to apoptosis

YB-1 facilitates basal and 5-fluorouracil-inducible expression of the human major vault protein (MVP) gene

The major vault protein is responsive to and interferes with interferon-γ-mediated STAT1 signals

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