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...
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Veröffentlicht in: | The Journal of cell biology 2003-11, Vol.163 (4), p.825 |
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creator | Sakaguchi, Masakiyo Miyazaki, Masahiro Takaishi, Mikiro Sakaguchi, Yoshihiko Makino, Eiichi Kataoka, Noriyuki Yamada, Hidenori Namba, Masayoshi Huh, Nam-ho |
description | 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. |
doi_str_mv | 10.1083/jcb.200304017 |
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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.</description><identifier>ISSN: 0021-9525</identifier><identifier>DOI: 10.1083/jcb.200304017</identifier><identifier>PMID: 14623863</identifier><language>eng</language><publisher>United States</publisher><subject>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 ; Nucleolin ; Phosphoproteins - metabolism ; Phosphorylation - drug effects ; Protein Binding - drug effects ; Protein Binding - physiology ; RNA-Binding Proteins - metabolism ; S100 Proteins - metabolism ; Sp1 Transcription Factor - metabolism</subject><ispartof>The Journal of cell biology, 2003-11, Vol.163 (4), p.825</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14623863$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sakaguchi, Masakiyo</creatorcontrib><creatorcontrib>Miyazaki, Masahiro</creatorcontrib><creatorcontrib>Takaishi, Mikiro</creatorcontrib><creatorcontrib>Sakaguchi, Yoshihiko</creatorcontrib><creatorcontrib>Makino, Eiichi</creatorcontrib><creatorcontrib>Kataoka, Noriyuki</creatorcontrib><creatorcontrib>Yamada, Hidenori</creatorcontrib><creatorcontrib>Namba, Masayoshi</creatorcontrib><creatorcontrib>Huh, Nam-ho</creatorcontrib><title>S100C/A11 is a key mediator of Ca(2+)-induced growth inhibition of human epidermal keratinocytes</title><title>The Journal of cell biology</title><addtitle>J Cell Biol</addtitle><description>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.</description><subject>Active Transport, Cell Nucleus - drug effects</subject><subject>Active Transport, Cell Nucleus - physiology</subject><subject>Animals</subject><subject>Antibodies - pharmacology</subject><subject>Binding, Competitive - physiology</subject><subject>Calcium - metabolism</subject><subject>Calcium - pharmacology</subject><subject>Calcium Signaling - physiology</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Differentiation - physiology</subject><subject>Cell Division - drug effects</subject><subject>Cell Division - physiology</subject><subject>Cell Line, Transformed</subject><subject>Cyclin-Dependent Kinase Inhibitor p21</subject><subject>Cyclins - metabolism</subject><subject>Epidermal Cells</subject><subject>Epidermis - growth & development</subject><subject>Epidermis - metabolism</subject><subject>Extracellular Fluid - drug effects</subject><subject>Extracellular Fluid - metabolism</subject><subject>Humans</subject><subject>Keratinocytes - cytology</subject><subject>Keratinocytes - drug effects</subject><subject>Keratinocytes - metabolism</subject><subject>Nucleolin</subject><subject>Phosphoproteins - metabolism</subject><subject>Phosphorylation - drug effects</subject><subject>Protein Binding - drug effects</subject><subject>Protein Binding - physiology</subject><subject>RNA-Binding Proteins - metabolism</subject><subject>S100 Proteins - metabolism</subject><subject>Sp1 Transcription Factor - metabolism</subject><issn>0021-9525</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1jztPwzAYAD2AaCmMrMgjCKX9_IjjjlVUHlIlBmAunx2buDQPOa5Q_j1FwHTL6aQj5IrBnIEWi501cw4gQAIrTsgUgLNsmfN8Qs6HYQcAspDijEyYVFxoJabk_YUBlIsVYzQMFOmnG2njqoCpi7TztMQbfnebhbY6WFfRj9h9pZqGtg4mpNC1P059aLClrg-Viw3uj42IKbSdHZMbLsipx_3gLv84I2_369fyMds8PzyVq03WM85TJr1FzrBgWnFbVE45YZWQXFVGcqmV10pLA14KdK7IjV8ieMMsOgGG51rMyPVvtz-Y48C2j6HBOG7_V8U3doZSwg</recordid><startdate>20031124</startdate><enddate>20031124</enddate><creator>Sakaguchi, Masakiyo</creator><creator>Miyazaki, Masahiro</creator><creator>Takaishi, Mikiro</creator><creator>Sakaguchi, Yoshihiko</creator><creator>Makino, Eiichi</creator><creator>Kataoka, Noriyuki</creator><creator>Yamada, Hidenori</creator><creator>Namba, Masayoshi</creator><creator>Huh, Nam-ho</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>20031124</creationdate><title>S100C/A11 is a key mediator of Ca(2+)-induced growth inhibition of human epidermal keratinocytes</title><author>Sakaguchi, Masakiyo ; 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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.</abstract><cop>United States</cop><pmid>14623863</pmid><doi>10.1083/jcb.200304017</doi></addata></record> |
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subjects | 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 Nucleolin Phosphoproteins - metabolism Phosphorylation - drug effects Protein Binding - drug effects Protein Binding - physiology RNA-Binding Proteins - metabolism S100 Proteins - metabolism Sp1 Transcription Factor - metabolism |
title | S100C/A11 is a key mediator of Ca(2+)-induced growth inhibition of human epidermal keratinocytes |
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