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

p27^<Kip1>在人胃癌转移中的作用

• 批准号: 14571189
• 负责人: KAMIYA Kinji
• 金额: $ 2.11万
• 依托单位: HAMAMATSU UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571189/
• 关键词: Ubiquitin ligase; p27^<Kip1>; procinosis; Cell cycle; gastric cancer; p27^<Kip1>; ユビキチン; Skp2; 大腸癌; p27^<kip1>ノックアウトヒトがん細胞; 腫瘍転移増殖能; マイクロアレイ

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>.

泛素-蛋白酶体途径是控制细胞内蛋白质水平的关键系统。该途径不仅负责短寿命蛋白质的降解，还负责肿瘤抑制因子、转录因子和细胞周期蛋白的降解。泛素-蛋白质连接酶决定泛素化的底物特异性。在本研究中，我们分析了Cdk抑制蛋白p27的蛋白水解降解的分子机制<Kip1>。在<Kip1>本研究中，我们发现，作为SCF-Skp 2泛素连接酶降解p27的一个亚组分，Cks 1通过泛素-蛋白酶体途径在肿瘤发生后受到调节。我们还发现Cks 1在人肺癌中高表达。因此，Cks 1蛋白质降解的改变被认为促进癌症的生长和恶性。接下来，我们使用p27 <Kip1>β表达下调的模型细胞系，实验证明p27 β表达下调促进了结小鼠中的肿瘤进展<Kip1>。

项目成果

北川雅敏: "現代医療36"現代医療社. 147-153 (2004)

北川正敏：《现代医疗36》现代医疗社147-153（2004）。

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