Introduction of an N-terminal peptide of S100C/A11 into human cells induces apoptotic cell death

Eiichi Makino, Masakiyo Sakaguchi, Keiji Iwatsuki, Nam Ho Huh

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

S100 proteins belong to the EF-hand Ca 2+-binding protein family and are involved in the regulation of a variety of cellular processes. Individual S 100 proteins are expressed in cell- and tissue-specific manners, and functional deterioration of S100 proteins leads to a number of human diseases, including cancer. We previously demonstrated that S100C/A11 was translocated to nuclei and inhibited DNA synthesis in human keratinocytes when exposed to high Ca 2+. In the present study we examined the effects of synthetic partial peptides of S100C/ All on human carcinoma cell lines. Only an N-terminal peptide with 19 amino acid residues (MAK19) showed cytotoxicity to the cell lines in dose- and time-dependent manners when introduced into cells by flanking the HIV-TAT protein transduction domain (TAT-MAK19). Pulse field electrophoresis revealed that DNA of the treated cells was partially degradated. Annexin V, a marker of cellular apoptosis, was detected in the cells treated with TAT-MAK19 by immunostaining and flow cytometry. The induction of apoptotic cell death was apparently independent of p53, p21 WAF1/C1P1, and caspase activity, but treatment with TAT-MAK19 resulted in partial translocation of apoptosis-inducing factor (AIF) from the cytoplasm to nuclei. These results indicate that MAK19 induces apoptosis in human cell lines and may therefore lead to the establishment of a new molecular target for the treatment of human cancer.

Original languageEnglish
Pages (from-to)612-620
Number of pages9
JournalJournal of Molecular Medicine
Volume82
Issue number9
DOIs
Publication statusPublished - Sep 2004

Fingerprint

Cell Death
S100 Proteins
Peptides
Cell Line
Apoptosis Inducing Factor
Apoptosis
Human Immunodeficiency Virus Proteins
EF Hand Motifs
Annexin A5
DNA
Caspases
Keratinocytes
Electrophoresis
Neoplasms
Flow Cytometry
Cytoplasm
Carcinoma
Amino Acids

Keywords

  • Apoptosis
  • Human cancer
  • P21
  • Peptide
  • S100C/A11

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Introduction of an N-terminal peptide of S100C/A11 into human cells induces apoptotic cell death. / Makino, Eiichi; Sakaguchi, Masakiyo; Iwatsuki, Keiji; Huh, Nam Ho.

In: Journal of Molecular Medicine, Vol. 82, No. 9, 09.2004, p. 612-620.

Research output: Contribution to journalArticle

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