Cell Growth Arrest by Sialic Acid Clusters in Ganglioside GM3 Mimetic Polymers
Ganglioside GM3, one of the sialic acid containing glycosphingolipids, is known to form clusters in lipid microdomains, which serve as platforms for effective signal transduction. In attempt to clarify the GM3 cluster effect, we enzymatically synthesized GM3 mimetic polymer (GM3-p), with an acrylami...
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Oxford University Press
2007
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Online Access: | http://glycob.oxfordjournals.org/cgi/content/short/cwm020v1 https://doi.org/10.1093/glycob/cwm020 |
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fthighwire:oai:open-archive.highwire.org:glycob:cwm020v1 2023-05-15T15:52:46+02:00 Cell Growth Arrest by Sialic Acid Clusters in Ganglioside GM3 Mimetic Polymers Uemura, Satoshi Feng, Fei Kume, Maya Yamada, Kuriko Kabayama, Kazuya Nishimura, Shin-ichiro Igarashi, Yasuyuki Inokuchi, Jin-ichi 2007-02-22 04:08:13.0 text/html http://glycob.oxfordjournals.org/cgi/content/short/cwm020v1 https://doi.org/10.1093/glycob/cwm020 en eng Oxford University Press http://glycob.oxfordjournals.org/cgi/content/short/cwm020v1 http://dx.doi.org/10.1093/glycob/cwm020 Copyright (C) 2007, Society for Glycobiology Article TEXT 2007 fthighwire https://doi.org/10.1093/glycob/cwm020 2013-05-27T08:00:17Z Ganglioside GM3, one of the sialic acid containing glycosphingolipids, is known to form clusters in lipid microdomains, which serve as platforms for effective signal transduction. In attempt to clarify the GM3 cluster effect, we enzymatically synthesized GM3 mimetic polymer (GM3-p), with an acrylamide backbone from LacCer mimetic polymer (LacCer-p). Interestingly, GM3-p, but not LacCer-p, reversibly inhibited proliferation of NIH3T3 cells, which are normally resistant to exogenously added GM3. Moreover, we found that the introduction of carbonic acid into the acrylamide chain aided well-oriented cluster formation and enhanced the inhibitory effect of GM3-p. Since sialyllactosyl polymer and GM4 mimetic polymer, but not GM2 mimetic polymer, also inhibited cell proliferation, sialic acid-galactose units must be essential for the biological activity of GM3-p. These results suggest that the formation of sialic acid-galactose clusters is necessary for the suppressive effect of GM3-p. GM3-p treatment did not affect the serum-dependent activation of ERK1/2 or c-fos expression, but caused a reduction in the gene and/or protein expression of cyclin D1, cyclin E, cdk4, and cdk2, which are involved in the cell cycle. Therefore, GM3-p inhibits cell proliferation by reducing cyclin D1-cdk4 and cyclin E-cdk2 complexes without affecting growth factor signaling from serum to c-fos. Text Carbonic acid HighWire Press (Stanford University) Glycobiology 17 6 568 577 |
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Article Uemura, Satoshi Feng, Fei Kume, Maya Yamada, Kuriko Kabayama, Kazuya Nishimura, Shin-ichiro Igarashi, Yasuyuki Inokuchi, Jin-ichi Cell Growth Arrest by Sialic Acid Clusters in Ganglioside GM3 Mimetic Polymers |
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Article |
description |
Ganglioside GM3, one of the sialic acid containing glycosphingolipids, is known to form clusters in lipid microdomains, which serve as platforms for effective signal transduction. In attempt to clarify the GM3 cluster effect, we enzymatically synthesized GM3 mimetic polymer (GM3-p), with an acrylamide backbone from LacCer mimetic polymer (LacCer-p). Interestingly, GM3-p, but not LacCer-p, reversibly inhibited proliferation of NIH3T3 cells, which are normally resistant to exogenously added GM3. Moreover, we found that the introduction of carbonic acid into the acrylamide chain aided well-oriented cluster formation and enhanced the inhibitory effect of GM3-p. Since sialyllactosyl polymer and GM4 mimetic polymer, but not GM2 mimetic polymer, also inhibited cell proliferation, sialic acid-galactose units must be essential for the biological activity of GM3-p. These results suggest that the formation of sialic acid-galactose clusters is necessary for the suppressive effect of GM3-p. GM3-p treatment did not affect the serum-dependent activation of ERK1/2 or c-fos expression, but caused a reduction in the gene and/or protein expression of cyclin D1, cyclin E, cdk4, and cdk2, which are involved in the cell cycle. Therefore, GM3-p inhibits cell proliferation by reducing cyclin D1-cdk4 and cyclin E-cdk2 complexes without affecting growth factor signaling from serum to c-fos. |
format |
Text |
author |
Uemura, Satoshi Feng, Fei Kume, Maya Yamada, Kuriko Kabayama, Kazuya Nishimura, Shin-ichiro Igarashi, Yasuyuki Inokuchi, Jin-ichi |
author_facet |
Uemura, Satoshi Feng, Fei Kume, Maya Yamada, Kuriko Kabayama, Kazuya Nishimura, Shin-ichiro Igarashi, Yasuyuki Inokuchi, Jin-ichi |
author_sort |
Uemura, Satoshi |
title |
Cell Growth Arrest by Sialic Acid Clusters in Ganglioside GM3 Mimetic Polymers |
title_short |
Cell Growth Arrest by Sialic Acid Clusters in Ganglioside GM3 Mimetic Polymers |
title_full |
Cell Growth Arrest by Sialic Acid Clusters in Ganglioside GM3 Mimetic Polymers |
title_fullStr |
Cell Growth Arrest by Sialic Acid Clusters in Ganglioside GM3 Mimetic Polymers |
title_full_unstemmed |
Cell Growth Arrest by Sialic Acid Clusters in Ganglioside GM3 Mimetic Polymers |
title_sort |
cell growth arrest by sialic acid clusters in ganglioside gm3 mimetic polymers |
publisher |
Oxford University Press |
publishDate |
2007 |
url |
http://glycob.oxfordjournals.org/cgi/content/short/cwm020v1 https://doi.org/10.1093/glycob/cwm020 |
genre |
Carbonic acid |
genre_facet |
Carbonic acid |
op_relation |
http://glycob.oxfordjournals.org/cgi/content/short/cwm020v1 http://dx.doi.org/10.1093/glycob/cwm020 |
op_rights |
Copyright (C) 2007, Society for Glycobiology |
op_doi |
https://doi.org/10.1093/glycob/cwm020 |
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Glycobiology |
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17 |
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6 |
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568 |
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577 |
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1766387861523791872 |