Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Proc Natl Acad Sci U S A. 2012 Aug 14;109(33):E2215-22. doi: 10.1073/pnas.1120517109. Epub 2012 Jul 9.
Aurora kinases are highly conserved, essential regulators of cell division. Two Aurora kinase isoforms, A and B (AURKA and AURKB), are expressed ubiquitously in mammals, whereas a third isoform, Aurora C (AURKC), is largely restricted to germ cells. Because AURKC is very similar to AURKB, based on sequence and functional analyses, why germ cells express AURKC is unclear. We report that Aurkc(-/-) females are subfertile, and that AURKB function declines as development progresses based on increasing severity of cytokinesis failure and arrested embryonic development. Furthermore, we find that neither Aurkb nor Aurkc is expressed after the one-cell stage, and that AURKC is more stable during maturation than AURKB using fluorescently tagged reporter proteins. In addition, Aurkc mRNA is recruited during maturation. Because maturation occurs in the absence of transcription, posttranscriptional regulation of Aurkc mRNA, coupled with the greater stability of AURKC protein, provides a means to ensure sufficient Aurora kinase activity, despite loss of AURKB, to support both meiotic and early embryonic cell divisions. These findings suggest a model for the presence of AURKC in oocytes: that AURKC compensates for loss of AURKB through differences in both message recruitment and protein stability.
极光激酶是高度保守的细胞分裂必需调节剂。两种极光激酶同工型，A 和 B（AURKA 和 AURKB），在哺乳动物中广泛表达，而第三种同工型，极光激酶 C（AURKC），主要局限于生殖细胞。由于 AURKC 在序列和功能上与 AURKB 非常相似，因此不清楚为什么生殖细胞表达 AURKC。我们报告说 Aurkc(-/-) 雌性是不育的，并且随着发育的进行，AURKB 的功能下降，基于越来越严重的胞质分裂失败和胚胎发育停滞。此外，我们发现 Aurkb 和 Aurkc 在单细胞阶段后都不表达，并且使用荧光标记的报告蛋白，AURKC 在成熟过程中比 AURKB 更稳定。此外，Aurkc mRNA 在成熟过程中被募集。由于成熟发生在没有转录的情况下，因此 Aurkc mRNA 的转录后调节，加上 AURKC 蛋白的更高稳定性，提供了一种手段，即使失去 AURKB，也能确保足够的极光激酶活性，以支持减数分裂和早期胚胎细胞分裂。这些发现为卵母细胞中存在 AURKC 提出了一个模型：AURKC 通过在 mRNA 募集和蛋白质稳定性方面的差异来补偿 AURKB 的缺失。
