S100C/A11 is a key mediator of Ca(2+)-induced growth inhibition of human epidermal keratinocytes.
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.
Sakaguchi
Masakiyo
M
Department of Cell Biology, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan.
Miyazaki
Masahiro
M
Takaishi
Mikiro
M
Sakaguchi
Yoshihiko
Y
Makino
Eiichi
E
Kataoka
Noriyuki
N
Yamada
Hidenori
H
Namba
Masayoshi
M
Huh
Nam-ho
NH
D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001667:Binding, Competitive / Q000502:physiology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D020013:Calcium Signaling / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002461:Cell Line, Transformed; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000254:growth & development* / Q000378:metabolism; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D016601:RNA-Binding Proteins / Q000378:metabolism; D009418:S100 Proteins / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000378:metabolism; D000097796:Nucleolin
D000906:Antibodies; D002118:Calcium; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D009418:S100 Proteins; D016329:Sp1 Transcription Factor; D000097796:Nucleolin; C493956:CDKN1A protein, human; C072337:S100A11 protein, human