S100C/A11 is a key mediator of Ca(2+)-induced growth inhibition of human epidermal keratinocytes

J Cell Biol. 2003 Nov 24;163(4):825-35. doi: 10.1083/jcb.200304017. Epub 2003 Nov 17.


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 p21CIP1/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 Ca(2+)-induced growth inhibition of human keratinocytes in culture, and that it may be possibly involved in the growth regulation in vivo as well.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / drug effects
  • Active Transport, Cell Nucleus / physiology
  • Animals
  • Antibodies / pharmacology
  • Binding, Competitive / physiology
  • Calcium / metabolism
  • Calcium / pharmacology
  • Calcium Signaling / physiology*
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology*
  • Cell Division / drug effects
  • Cell Division / physiology
  • Cell Line, Transformed
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / metabolism
  • Epidermal Cells
  • Epidermis / growth & development*
  • Epidermis / metabolism
  • Extracellular Fluid / drug effects
  • Extracellular Fluid / metabolism
  • Humans
  • Keratinocytes / cytology
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism*
  • Phosphoproteins / metabolism
  • Phosphorylation / drug effects
  • Protein Binding / drug effects
  • Protein Binding / physiology
  • RNA-Binding Proteins / metabolism
  • S100 Proteins / metabolism*
  • Sp1 Transcription Factor / metabolism


  • Antibodies
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Phosphoproteins
  • RNA-Binding Proteins
  • S100 Proteins
  • Sp1 Transcription Factor
  • nucleolin
  • S100A11 protein, human
  • Calcium