S100C/A11 is a key mediator of Ca2+-induced growth inhibition of human epidermal keratinocytes

Masakiyo Sakaguchi, Masahiro Miyazaki, Mikiro Takaishi, Yoshihiko Sakaguchi, Eiichi Makino, Noriyuki Kataoka, Hidenori Yamada, Masayoshi Namba, Nam Ho Huh

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95 Citations (Scopus)

Abstract

An increase in extracellular Ca2+ induces growth arrest and differentiation of human keratinocytes in culture. We examined possible involvement of S100C/A11 in this growth regulation. On exposure of the cells to high Ca2+ S100C/A11 was specifically phosphorylated at 10Thr and 94Ser. Phosphorylation facilitated the binding of S100C/A11 to nucleolin, resulting in nuclear translocation of S100C/A11. In nuclei, S100C/A11 liberated Sp1/3 from nucleolin. The resulting free Sp1/3 transcriptionally activated p21CIP1/WAF1, a representative negative regulator of cell growth. Introduction of anti-S100C/A11 antibody into the cells largely abolished the growth inhibition induced by Ca2+ and the induction of p21CIP/WAF1. In the human epidermis, S100C/A11 was detected in nuclei of differentiating cells in the suprabasal layers, but not in nuclei of proliferating cells in the basal layer. These results indicate that S100C/A11 is a key mediator of the Ca2+-induced growth inhibition of human keratinocytes in culture, and that it may be possibly involved in the growth regulation in vivo as well.

Original languageEnglish
Pages (from-to)825-835
Number of pages11
JournalJournal of Cell Biology
Volume163
Issue number4
DOIs
Publication statusPublished - Nov 24 2003

Keywords

  • Calcium
  • Keratinocyte
  • Nucleolin
  • P21
  • Sp1

ASJC Scopus subject areas

  • Cell Biology

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    Sakaguchi, M., Miyazaki, M., Takaishi, M., Sakaguchi, Y., Makino, E., Kataoka, N., Yamada, H., Namba, M., & Huh, N. H. (2003). S100C/A11 is a key mediator of Ca2+-induced growth inhibition of human epidermal keratinocytes. Journal of Cell Biology, 163(4), 825-835. https://doi.org/10.1083/jcb.200304017