A small upstream open reading frame causes inhibition of human major vault protein expression from a ubiquitous mRNA splice variant

@article{Holzmann2001ASU,
  title={A small upstream open reading frame causes inhibition of human major vault protein expression from a ubiquitous mRNA splice variant},
  author={Klaus Holzmann and Ingo Ambrosch and Leonilla Elbling and Michael Micksche and Walter Berger},
  journal={FEBS Letters},
  year={2001},
  volume={494}
}
Overexpression of the major vault protein (MVP) has been linked to a multidrug resistance (MDR) phenotype. We describe a ubiquitously expressed MVP mRNA splice variant (long (L)‐MVP) differing from the regular isoform (short (S)‐MVP) within the 5′‐leader. Only L‐MVP mRNA contains a small upstream open reading frame which was proven to inhibit in vitro and in vivo MVP expression in cis. L‐MVP represented an almost constant portion of total MVP mRNA in diverse normal tissues, but was more… Expand
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References

SHOWING 1-10 OF 27 REFERENCES
Cloning and initial analysis of the human multidrug resistance-related MVP/LRP gene promoter.
TLDR
DNA sequences upstream to the transcription initiation site of the MVP gene in the human non-small cell lung cancer cell line SW-1573 are characterized and show strong promoter activity in chloramphenicol acetyltransferase (CAT) reporter assays. Expand
Role of two upstream open reading frames in the translational control of oncogene mdm2
TLDR
These results are consistent with a model in which overexpression of MDM2 in certain tumors results from a change in mRNA structure due to a switch in promoter usage. Expand
Translational Control by an Upstream Open Reading Frame in the HER-2/neu Transcript*
TLDR
The results suggest that the HER-2 uORF controls synthesis of this oncoprotein by limiting ribosomal access to downstream initiation sites. Expand
The role of the 5' untranslated region of an mRNA in translation regulation during development.
TLDR
This review focuses on 5' UTRs whose activity is regulated, the processes during which this regulation occurs, and as far as known the mechanisms involved. Expand
Vaults Are Up-regulated in Multidrug-resistant Cancer Cell Lines*
TLDR
The observation that vault synthesis is linked directly to multidrug resistance supports a direct role for vaults in drug resistance. Expand
The drug resistance-related protein LRP is the human major vault protein
TLDR
The cloning and chromosome localization of the gene coding for the LRP protein is described and the deduced LRP amino acid sequence shows 87.7% identity with the 104-kD rat major vault protein. Expand
The Inhibitory Upstream Open Reading Frame from Mammalian S-Adenosylmethionine Decarboxylase mRNA Has a Strict Sequence Specificity in Critical Positions*
TLDR
The mammalian AdoMetDCuORF inhibits downstream translation when placed into the 5′ leader of a yeast mRNA with characteristics resembling those in mammalian cells, suggesting that the encoded peptide has a similar target across species. Expand
Modulation of translation by the 5' leader sequence of the mRNA encoding murine tissue inhibitor of metalloproteinases.
TLDR
TIMP synthesized in vitro was translated 3-fold more efficiently from the 5'-truncated transcript, consistent with the possibility that induction of shorter, more efficiently translated, TIMP transcripts are an important means of amplifying TIMP expression in response to serum. Expand
Disruption of Ribosomal Scanning on the 5′-Untranslated Region, and Not Restriction of Translational Initiation per se, Modulates the Stability of Nonaberrant mRNAs in the Yeast Saccharomyces cerevisiae*
TLDR
The mechanisms by which the 5′-untranslated region (UTR) of nonaberrant mRNAs acts to modulate both translation and mRNA decay in Saccharomyces cerevisiae are examined. Expand
A cis-acting element in the BCL-2 gene controls expression through translational mechanisms.
TLDR
Findings suggest that the uORF located within the 5'UTR of the bcl-2 gene is necessary and sufficient for translational regulation of bcl -2 gene expression. Expand
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