5-Fluorouracil Activation of p53 Involves an MDM2-Ribosomal Protein Interaction

作者: Xiao-Xin Sun , Mu-Shui Dai , Hua Lu

DOI: 10.1074/JBC.M610621200

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摘要: 5-fluorouracil (5-FU) is a widely used chemotherapeutic drug for the treatment of variety solid tumors. The anti-tumor activity 5-FU has been attributed in part to its ability induce p53-dependent cell growth arrest and apoptosis. However, molecular mechanisms underlying p53 activation by remain largely obscure. Here we report that leads stabilization blocking MDM2 feedback inhibition through ribosomal proteins. increased fraction ribosome-free L5, L11, L23 proteins their interaction with MDM2, leading G1/S arrest. Conversely, individual knockdown these small interfering RNA prevented 5-FU-induced reversed These results demonstrate triggers stress response so are released from ribosome activate ablating MDM2-p53 circuit.

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