Abstract
Protein transduction therapy using poly-arginine can deliver the bioactive p53 protein into cancer cells and inhibits the proliferation of the cells. However, one disadvantage of such therapy is the short intracellular half-life of the delivered protein. Here, we generated mutant proteins in which multiple lysine residues in the C-terminal were substituted by arginines. The mutant proteins were effectively delivered in glioma cells and were resistant to Mdm2-mediated ubiquitination. Moreover, the mutant proteins displayed higher transcription regulatory activity and powerful inhibition of the proliferation of glioma cells. These results suggest that ubiquitination-resistant p53 protein therapy may become a new effective cancer therapy.
Original language | English |
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Pages (from-to) | 3965-3969 |
Number of pages | 5 |
Journal | FEBS Letters |
Volume | 579 |
Issue number | 18 |
DOIs | |
Publication status | Published - Jul 18 2005 |
Keywords
- Brain tumor
- Gene therapy
- Poly-arginine
- TAT
- p53
ASJC Scopus subject areas
- Biophysics
- Structural Biology
- Biochemistry
- Molecular Biology
- Genetics
- Cell Biology