Regulation of degradation of p27Kip1, one of CDK inhibitory protein, for cancer therapy

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It has been reported that the cyclin dependent kinase inhibitory proteins (CDK inhibitor) , such as p27ィイD1Kip1ィエD1 negatively regulates the G1-CDK activity in normal cells. In most cancer cells, up-regulation of G1-cyclin dependent kinase (G1-CDK) activity contributes in their malignant growth. First of all, we study the expression of p27ィイD1Kip1ィエD1 in human lung cancer using immunohistoichemistry. We found that p27ィイD1Kip1ィエD1 labeling index was decreased and p27ィイD1Kip1ィエD1 degradation activity was up-regulated in cancerious lung tissues, compared with nonneoplastic lung tissues. Therefore, it is important to study the mechanisms of p27ィイD1Kip1ィエD1 degradation. In the next study, we found that p27ィイD1Kip1ィエD1 was eliminated by two independent mechanisms, ubiquitin-mediated degradation and ubiquitin-independent processing. These tow activity was significantly high during progression from G1 to S phase. These finding suggested that inhibitor of p27ィイD1Kip1ィエD1 degradation is a potential drug for cancer therapy.