The role of p27(Kip1) phosphorylation at serine 10 in the migration of malignant glioma cells in vitro.
Until recently, Cip/Kip members were almost solely viewed as nuclear proteins with a principal function of inhibiting cyclin/cyclin dependent kinase (CDK) activity and hence, inhibiting cell cycle progression. P27(Kip1) (hereafter p27) belongs to the Cip/Kip family that binds and inhibits all the cyclin/CDK complexes, thus often referred as a universal CDK inhibitor. However, emerging studies now suggest that Cip/Kip proteins play additional roles outside of the nucleus. Indeed, previous reports have linked p27 to the regulation of actin dynamics and cell migration. In this study, we constructed a model of migration-activated glioma cells by using the migration-stimulating substrate, a kind of ECM, laminin in vitro. Our results present evidence that laminin drives glioma cell migration without altering cell proliferation. Further, actively migrating cells which expressioned high phosphorylation of p27 at Ser10, and induced its cytoplasmic localization. In this process, Jab1 and CRM1 were also involved. Thus phosphorylation of p27 at Ser10 is necessary for both cytoplasmic localization and induction of cell migration. These observations solidified a genetic role of p27 in cell migration and this was independent of cyclin/CDK inhibition. Eventually, we transiently transfected p27S10A into T98G glioma cells, found that overexpression of p27S10A inhibited cell migration but not cell proliferation. These data linked phosphorylation of p27 at Ser10 and cell motility. Therefore, the major phosphorylation site at Ser10 of p27 played a pivotal role in the migration of malignant glioma cells.
Department of Pathology, Medical College, Nantong University, nantong, Jiangsu, 226011, P.R. China.
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D
Wang
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He
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Zhang
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Zhang
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Wang
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Qian
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Pan
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Meng
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Peng
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Shen
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Chen
D001932:Brain Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D005910:Glioma / Q000473:pathology*; D006801:Humans; D007797:Laminin / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000502:physiology; D012694:Serine / Q000378:metabolism
D050760:Cyclin-Dependent Kinase Inhibitor p27; D007797:Laminin; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D012694:Serine; C436291:CDKN1B protein, human