The NH2 terminus of influenza virus hemagglutinin-2 subunit peptides enhances the antitumor potency of polyarginine-mediated p53 protein transduction

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

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

Protein transduction therapy is a newly developing method that allows proteins, peptides, and biologically active compounds to penetrate across the plasma membrane by being fused with cell-penetrating peptides such as polyarginine. Polyarginine-fused p53 protein penetrates across the plasma membrane of cancer cells and inhibits the growth of the cells. However, the protein is often entrapped inside macropinosomes in the cytoplasm. Therefore, high dose concentrations of the protein are needed for it to function effectively. To overcome this problem, in the present study, polyarginine-fused p53 was linked with the NH2-terminal domain of influenza virus hemagglutinin-2 subunit (HA2), which is a pH-dependent fusogenic peptide that induces the lysis of membranes at low pH levels. The protein was capable of efficiently translocating into the nucleus of glioma cells and induced p21 WAF1 transcriptional activity more effectively than did polyarginine-fused p53 protein. Moreover, low concentrations of the protein significantly inhibited the growth of cancer cells. These results suggest that protein transduction therapy using polyarginine and HA2 may be useful as a method for cancer therapy.

Original languageEnglish
Pages (from-to)8285-8289
Number of pages5
JournalJournal of Biological Chemistry
Volume280
Issue number9
DOIs
Publication statusPublished - Mar 4 2005

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Hemagglutinins
Orthomyxoviridae
Viruses
Peptides
Proteins
Cells
Cell membranes
Cell Membrane
Cell-Penetrating Peptides
polyarginine
Neoplasms
Growth
Cell Nucleus
Glioma
Cytoplasm
Therapeutics
Membranes

ASJC Scopus subject areas

  • Biochemistry

Cite this

The NH2 terminus of influenza virus hemagglutinin-2 subunit peptides enhances the antitumor potency of polyarginine-mediated p53 protein transduction. / Michiue, Hiroyuki; Tomizawa, Kazuhito; Wei, Fan Yan; Matsushita, Masayuki; Lu, Yun Fei; Ichikawa, Tomotsugu; Tamiya, Takashi; Date, Isao; Matsui, Hideki.

In: Journal of Biological Chemistry, Vol. 280, No. 9, 04.03.2005, p. 8285-8289.

Research output: Contribution to journalArticle

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