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 1 2004

Keywords

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

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Introduction of an N-terminal peptide of S100C/A11 into human cells induces apoptotic cell death'. Together they form a unique fingerprint.

  • Cite this