Transforming Growth Factor β1 Increases the Stability of p21/WAF1/CIP1 Protein and Inhibits CDK2 Kinase Activity in Human Colon Carcinoma FET Cells

作者: Michael G. Brattain , Tien C. Ko , Sudhakar Ammanamanchi , Jian Gen Gong

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摘要: We examined transforming growth factor-β1 (TGF-β1) effects on cell cycle progression of human colon carcinoma FET cells. TGF-β1 inhibited DNA synthesis and cyclin-dependent kinase (CDK) activity after release from arrest in association with induction the p21 CDK inhibitor, whereas cyclins, CDKs, p27 protein levels remained relatively unchanged. The decrease CDK2 was result increased cyclin A-CDK2 E-CDK2. treatment late G 1 showed reduced synthesis. Consequently, early is critical for inhibition activity. Although treatments failed to induce protein, mRNA observed S phase. Further analysis that increases stability throughout phases cycle. Our results demonstrate stimulation regulated at posttranscriptional transcriptional levels. This a novel mechanism requiring stabilization which binds inhibits E-CDK2 rather than direct modulation or as seen other systems.

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