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 |
|---|---|
| Pages (from-to) | 3965-3969 |
| Number of pages | 5 |
| Journal | FEBS Letters |
| Volume | 579 |
| Issue number | 18 |
| DOIs | |
| Publication status | Published - Jul 18 2005 |
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Keywords
- Brain tumor
- Gene therapy
- p53
- Poly-arginine
- TAT
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Molecular Biology
Cite this
Ubiquitination-resistant p53 protein transduction therapy facilitates anti-cancer effect on the growth of human malignant glioma cells. / Michiue, Hiroyuki; Tomizawa, Kazuhito; Matsushita, Masayuki; Tamiya, Takashi; Lu, Yun Fei; Ichikawa, Tomotsugu; Date, Isao; Matsui, Hideki.
In: FEBS Letters, Vol. 579, No. 18, 18.07.2005, p. 3965-3969.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Ubiquitination-resistant p53 protein transduction therapy facilitates anti-cancer effect on the growth of human malignant glioma cells
AU - Michiue, Hiroyuki
AU - Tomizawa, Kazuhito
AU - Matsushita, Masayuki
AU - Tamiya, Takashi
AU - Lu, Yun Fei
AU - Ichikawa, Tomotsugu
AU - Date, Isao
AU - Matsui, Hideki
PY - 2005/7/18
Y1 - 2005/7/18
N2 - 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.
AB - 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.
KW - Brain tumor
KW - Gene therapy
KW - p53
KW - Poly-arginine
KW - TAT
UR - http://www.scopus.com/inward/record.url?scp=21844477537&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=21844477537&partnerID=8YFLogxK
U2 - 10.1016/j.febslet.2005.06.021
DO - 10.1016/j.febslet.2005.06.021
M3 - Article
C2 - 15996664
AN - SCOPUS:21844477537
VL - 579
SP - 3965
EP - 3969
JO - FEBS Letters
JF - FEBS Letters
SN - 0014-5793
IS - 18
ER -