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首页> 外文期刊>Molecular and Cellular Biology >Phosphorylation and Stabilization of HURP by Aurora-A: Implication of HURP as a Transforming Target of Aurora-A
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Phosphorylation and Stabilization of HURP by Aurora-A: Implication of HURP as a Transforming Target of Aurora-A

机译:Aurora-A对HURP的磷酸化和稳定作用:HURP作为Aurora-A转化靶标的意义

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Aurora-A, a mitotic serine/threonine kinase with oncogene characteristics, has recently drawn intense attention because of its association with the development of human cancers and its relationship with mitotic progression. Using the gene expression profiles of Aurora-A as a template to search for and compare transcriptome expression profiles in publicly accessible microarray data sets, we identified HURP (encodes hepatoma upregulated protein) as one of the best Aurora-A-correlated genes. Empirical validation indicates that HURP has several characteristics in common with Aurora-A. These two genes have similar expression patterns in hepatocellular carcinoma, liver regeneration after partial hepatectomy, and cell cycle progression and across a variety of tissues and cell lines. Moreover, Aurora-A phosphorylated HURP in vitro and in vivo. Ectopic expression of either the catalytically inactive form of Aurora-A or the HURP-4P mutant, in which the Aurora-A phosphorylation sites were replaced with Ala, resulted in HURP instability and complex disassembly. In addition, HURP-wild-type stable transfectants were capable of growing in low-serum environments whereas HURP-4P grew poorly under low-serum conditions and failed to proliferate. These studies together support the view that the ability to integrate evidence derived from microarray studies into biochemical analyses may ultimately augment our predictive power when analyzing the potential role of poorly characterized proteins. While this combined approach was simply an initial attempt to answer a range of complex biological questions, our findings do suggest that HURP is a potential oncogenic target of Aurora-A.
机译:具有癌基因特征的有丝分裂丝氨酸/苏氨酸激酶Aurora-A最近因其与人类癌症的发展以及与有丝分裂进展的关系而备受关注。使用 Aurora - A 的基因表达谱作为模板,在公共可访问的微阵列数据集中搜索和比较转录组表达谱,我们确定了 HURP (编码肝癌上调蛋白)是最好的 Aurora - A 相关基因之一。经验验证表明, HURP 具有与 Aurora - A 相同的几个特征。这两个基因在肝细胞癌,部分肝切除术后的肝再生以及细胞周期进程以及跨各种组织和细胞系的表达模式相似。此外,Aurora-A在体外和体内都磷酸化了HURP。 Aurora-A或HURP-4P突变体的催化失活形式的异位表达(其中Aurora-A磷酸化位点被Ala取代)导致HURP不稳定和复杂的分解。此外,HURP野生型稳定转染子能够在低血清环境中生长,而HURP-4P在低血清条件下生长较差并且不能增殖。这些研究共同支持这样一种观点,即将微阵列研究得出的证据整合到生化分析中的能力最终可能会在分析特征不充分的蛋白质的潜在作用时最终增强我们的预测能力。虽然这种组合方法只是回答一系列复杂生物学问题的最初尝试,但我们的发现确实表明HURP是Aurora-A的潜在致癌靶标。

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