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

Oncogene. 2005 May 19;24(22):3606-18. doi: 10.1038/sj.onc.1208386.


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-MDR-related 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 time-dependent 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-FU-induced MVP promoter activity. Therefore, YB-1 is directly linked to MVP-mediated drug resistance.

MeSH terms

  • Antimetabolites, Antineoplastic / pharmacology*
  • Colonic Neoplasms / metabolism
  • DNA-Binding Proteins / drug effects
  • DNA-Binding Proteins / metabolism*
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm / physiology*
  • Electrophoretic Mobility Shift Assay
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Fluorouracil / pharmacology*
  • Humans
  • Immunohistochemistry
  • Nuclear Proteins
  • Promoter Regions, Genetic
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vault Ribonucleoprotein Particles / drug effects*
  • Vault Ribonucleoprotein Particles / genetics
  • Vault Ribonucleoprotein Particles / metabolism
  • Y-Box-Binding Protein 1


  • Antimetabolites, Antineoplastic
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Vault Ribonucleoprotein Particles
  • Y-Box-Binding Protein 1
  • YBX1 protein, human
  • major vault protein
  • Fluorouracil