Ubiquitination-resistant p53 protein transduction therapy facilitates anti-cancer effect on the growth of human malignant glioma cells

Hiroyuki Michiue, Kazuhito Tomizawa, Masayuki Matsushita, Takashi Tamiya, Yun Fei Lu, Tomotsugu Ichikawa, Isao Date, Hideki Matsui

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

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 languageEnglish
Pages (from-to)3965-3969
Number of pages5
JournalFEBS Letters
Volume579
Issue number18
DOIs
Publication statusPublished - 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

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