Roles of p27^<Kip1> on metastasis of human gastric cancers

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Ubiquitin-proteasome pathway is a key system that controls cellular levels of number of proteins. This pathway is responsible not only for the degradation of short-lived proteins but also tumor suppressors, transcription factors and cell cycle proteins. Ubiquitin-protein ligases determine the substrate specificity of ubiquitination. In this study, we analyzed the molecular mechanisms of proteolytic degradation of Cdk inhibitory protein p27^<Kip1>. Furthermore, we tried to experimentally demonstrate that down-regulation of p27^<Kip1> promoted tumor progression.In this study, we found that Cks1, a subcomponent of SCF-Skp2 ubiquitin ligase for p27-degradation, was post-translationally regulated by ubiquitin-proteasome pathway. We also found high expression of Cks1 in human lung cancers. Therefore, altered degradation of Cks1 proteins is thought to promote growth and malignancy of cancer. Next, we experimentally demonstrate that down-regulation of p27^<Kip1> promoted tumor progression in node mice using the model cell lines which shawed down-regulated expression of p27^<Kip1>.