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J Biol Chem. 2011 Mar 4;286(9):6911-7. doi: 10.1074/jbc.M110.194662. Epub 2010 Dec 14.

Conditional modulation of membrane protein expression in cultured cells mediated by prion protein recognition of short phosphorothioate oligodeoxynucleotides.

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1
Institute of Biochemistry, Food Science and Nutrition Food and Environmental Quality Sciences, Faculty of Agriculture, Hebrew University of Jerusalem, Rehovot 76100, Israel. mvkarpuj@gmail.com

Abstract

We demonstrate that the levels of native as well as transfected prion protein (PrP) are lowered in various cell lines exposed to phosphorothioate oligodeoxynucleotides (PS-DNA) and can be rapidly reverted to their normal amounts by removal of PS-DNA. This transient modulation was independent of the glycosylation state of PrP, and in addition, all three PrP glycoforms were susceptible to PS-DNA treatment. Deletion of the N-terminal domain (amino acids 23-99), but not of the other domains of PrP, abrogated its PS-DNA-mediated down-regulation. PrP versions localized in the mitochondria, cytoplasm, or nucleus were not modulated by PS-DNA, indicating that PrP surface exposure is required for executing this effect. Proteins that in their native forms were not responsive to PS-DNA, such as thymocyte antigen 1 (Thy1), Doppel protein (Dpl), green fluorescent protein (GFP), and cyan fluorescent protein (CFP), became susceptible to PS-DNA-mediated down-regulation following introduction of the N terminus of PrP into their sequence. These observations demonstrate the essential role of the N-terminal domain for promoting oligonucleotide-mediated reduction of the PrP level and suggest that transient treatment of cultured cells with PS-DNA may provide a general method for targeted modulation of the levels of desired surface proteins in a conditional and reversible manner.

PMID:
21156803
PMCID:
PMC3044946
DOI:
10.1074/jbc.M110.194662
[Indexed for MEDLINE]
Free PMC Article
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