Over-expression of Aurora-A targets cytoplasmic polyadenylation element binding protein and promotes mRNA polyadenylation of Cdk1 and cyclin B1
Over-expression of Aurora-A targets cytoplasmic polyadenylation element binding protein and promotes mRNA polyadenylation of Cdk1 and cyclin B1
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DOI：
10.1111/j.1365-2443.2005.00870.x
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发表时间：
2005-07-01
期刊：
影响因子：
2.1
通讯作者：
Hirota, T
中科院分区：
文献类型：
--
作者：
Sasayama, T;Marumoto, T;Hirota, T
极光-A是一种中心体丝氨酸-苏氨酸激酶，调节有丝分裂。Aurora-A的过度表达广泛存在于多种肿瘤中，与肿瘤的发生发展密切相关。然而，Aurora-A的过度表达如何促进癌症的发生仍不清楚。对乳腺肿瘤的免疫组织化学分析表明，Aurora-A的过度表达不仅限于中心体，还存在于细胞质中。这个过度表达的Aurora-A似乎在Thr288上被磷酸化，这是其酶激活所必需的。类似于Aurora-A在卵母细胞成熟和早期胚胎细胞周期中的作用，我们在这里研究了异位过表达的Aurora-A是否可以通过与人细胞质多腺化元件结合蛋白h-CPEB的同源基因相互作用来类似地刺激人体细胞培养细胞中mRNA的多腺苷化。体外实验显示Aurora-A直接与h-CPEB结合并磷酸化h-CPEB。我们发现，当Aurora-A和h-CPEB过表达时，Cyclin B1和CDK1的mRNA尾部的多聚腺苷化被协同刺激，并且在Aurora-A激动剂Ajuba的存在下进一步促进。我们的结果提示，异位过表达的Aurora-A的功能可能与癌症的发生有关。
Aurora-A is a centrosomal serine-threonine kinase that regulates mitosis. Over-expression of Aurora-A has been found in a wide range of tumors and has been implicated in oncogenic transformation. However, how Aurora-A over-expression contributes to promotion of carcinogenesis remains elusive. Immunohistochemical analysis of breast tumors revealed that over-expressed Aurora-A is not restricted to the centrosomes but is also found in the cytoplasm. This over-expressed Aurora-A appeared to be phosphorylated on Thr288, which is known to be required for its enzymatic activation. In analogy to Aurora-A's role in oocyte maturation and the early embryonic cell cycle, here we investigated whether ectopically over-expressed Aurora-A can similarly stimulate polyadenylation of mRNA in human somatic cultured cells by interacting with a human ortholog of cytoplasmic polyadenylation element binding protein, h-CPEB. In vitro experiments revealed that Aurora-A binds directly to, and phosphorylates, h-CPEB. We found that polyadenylation of mRNA tails of cyclin B1 and Cdk1 was synergistically stimulated when Aurora-A and h-CPEB were over-expressed, and they were further promoted in the presence of an Aurora-A activator Ajuba. Our results suggest a function of ectopically over-expressed Aurora-A that might be relevant for carcinogenesis.