[Activator of metastasis in cancer cells, Mst1/S100A4 protein binds to tumor suppressor protein p53].
This study for the first time demonstrates a physical and functional interaction between the Ca(2+)-binding protein Mts1/S100A4 and tumor suppressor p53 protein. Using different in vitro and in vivo approaches, we have found that Mts1 can bind to the C-terminal regulatory domain of p53. The Mts1 binding to p53 promotes activation of the reporter gene transcription in vivo. A modulation of the p53 target gene (p21/WAF, bax, mdm-2, and thrombospondin-1) expression was observed upon Mts1 induction in the cells expressing the wild-type p53. These results suggest that the ability of Mts1 to enhance p53-dependent apoptosis of tumor cells leads to the decrease/disappearance of the tumor cells expressing the wild-type p53. Thus, Mts1 promotes selection of more aggressive, metastatic phenotype during tumor progression.
Grigorian
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Institute of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark.
Lukanidin
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D000818:Animals; D017209:Apoptosis / Q000235:genetics; D056746:Cyclin G; D056766:Cyclin G1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D009154:Mutation; D009362:Neoplasm Metastasis / Q000235:genetics*; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D051736:Proto-Oncogene Proteins c-mdm2; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism*; D019700:Thrombospondin 1 / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; C494827:Bax protein, mouse; C534702:CCNG1 protein, human; C493956:CDKN1A protein, human; C534703:Ccng1 protein, mouse; C493957:Cdkn1a protein, mouse; D056746:Cyclin G; D056766:Cyclin G1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C470944:S100a4 protein, mouse; D019700:Thrombospondin 1; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C077591:S100A4 protein, human; C497206:MDM2 protein, human; C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2