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	J. Cell Biol. Nov (2003); 163(4):825-35
S100C/A11 is a key mediator of Ca(2+)-induced growth inhibition of human epidermal keratinocytes.
Sakaguchi M, Miyazaki M, Takaishi M, Sakaguchi Y, Makino E, Kataoka N, Yamada H, Namba M, Huh NH
Department of Cell Biology, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan.
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 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.
[PUBMED: 14623863]