Cancer: Mdm2-regulated stabilization of HuR by neddylation in HCC and colon cancer--a possible target for therapy.
Cancer: Mdm2-regulated stabilization of HuR by neddylation in HCC and colon cancer--a possible target for therapy.
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DOI：
10.1038/nrgastro.2011.241
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发表时间：
2011-12-13
期刊：
影响因子：
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通讯作者：
McLarnon, Andy
中科院分区：
文献类型：
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作者：
McLarnon, Andy
西班牙生物科学合作研究中心（CIC bioGUNE）的Maria Martinez-Chantar及其同事此前曾表明，HuR控制着肝细胞的增殖和分化。“我们认为HCC中HuR水平的增加可能是恶性转化的标志，”Martinez-Chantar解释说。现在，研究人员已经发现了控制HuR表达的关键途径。Neddylation通过将蛋白质与NEDD 8结合来稳定蛋白质。Mdm 2水平升高，促进neddylation，与HCC和转移性结肠癌中HuR表达增加相关，表明Mdm 2-NEDD 8-HuR通路可以调节恶性转化。研究人员现在正在各种病因的HCC中探索这种机制（图片）。他们还计划测试一种阻止NEDD 8激活的药物，因此可能会破坏导致HuR过表达的机制。
Maria Martinez-Chantar and colleagues, at the Center for Cooperative Research in Biosciences (CIC bioGUNE), Spain, had previously shown that HuR controls proliferation and differentiation of liver cells.“We thought that the increased levels of HuR in HCC could be a hallmark of malignant transformation,” explains Martinez-Chantar. Now the researchers have uncovered a key pathway that controls HuR expression. Neddylation stabilizes proteins by conjugating them to NEDD8. Raised levels of Mdm2, which promotes neddylation, correlated with increased HuR expression in HCC and metastatic colon cancer, suggesting that the Mdm2–NEDD8–HuR pathway could regulate malignant transformation. The researchers are now exploring this mechanism in HCC of various etiologies (image). They also plan to test a drug that prevents the activation of NEDD8 and could, therefore, disrupt the mechanism that leads to HuR overexpression.