Sasayama Takashi, Marumoto Tomotoshi, Kunitoku Naoko, Zhang Dongwei, Tamaki Norihiko, Kohmura Eiji, Saya Hideyuki, Hirota Toru
Department of Tumor Genetics and Biology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
Genes Cells. 2005 Jul;10(7):627-38. doi: 10.1111/j.1365-2443.2005.00870.x.
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.
极光激酶A是一种中心体丝氨酸 - 苏氨酸激酶，可调节有丝分裂。在多种肿瘤中均发现极光激酶A过表达，且其与致癌转化有关。然而，极光激酶A过表达如何促进癌症发生仍不清楚。对乳腺肿瘤的免疫组织化学分析显示，过表达的极光激酶A不仅局限于中心体，在细胞质中也有发现。这种过表达的极光激酶A似乎在苏氨酸288位点发生了磷酸化，而这是其酶激活所必需的。类似于极光激酶A在卵母细胞成熟和早期胚胎细胞周期中的作用，我们在此研究了异位过表达的极光激酶A是否能通过与细胞质聚腺苷酸化元件结合蛋白的人类同源物h - CPEB相互作用，同样刺激人类体细胞培养细胞中mRNA的聚腺苷酸化。体外实验表明，极光激酶A直接结合并磷酸化h - CPEB。我们发现，当极光激酶A和h - CPEB过表达时，细胞周期蛋白B1和细胞周期蛋白依赖性激酶1的mRNA尾巴聚腺苷酸化受到协同刺激，并且在极光激酶A激活剂Ajuba存在的情况下进一步增强。我们的结果表明异位过表达的极光激酶A的一种功能可能与致癌作用相关。
