Sasai K, Parant J M, Brandt M E, Carter J, Adams H P, Stass S A, Killary A M, Katayama H, Sen S
Department of Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Oncogene. 2008 Jul 3;27(29):4122-7. doi: 10.1038/onc.2008.47. Epub 2008 Mar 17.
Aurora A (also known as STK15/BTAK in humans), a putative oncoprotein naturally overexpressed in many human cancers, is a member of the conserved Aurora protein serine/threonine kinase family that is implicated in the regulation of G(2)-M phases of the cell cycle. In vitro studies utilizing antibody microinjection, siRNA silencing and small molecule inhibitors have indicated that Aurora A functions in early as well as late stages of mitosis. However, due to limitations in specificity of the techniques, exact functional roles of the kinase remain to be clearly elucidated. In order to identify the physiological functions in vivo, we have generated Aurora A null mouse embryos, which show severe defects at 3.5 d.p.c. (days post-coitus) morula/blastocyst stage and lethality before 8.5 d.p.c. Null embryos at 3.5 d.p.c. reveal growth retardation with cells in mitotic disarray manifesting disorganized spindle, misaligned and lagging chromosomes as well as micronucleated cells. These findings provide the first unequivocal genetic evidence for an essential physiological role of Aurora A in normal mitotic spindle assembly, chromosome alignment segregation and maintenance of viability in mammalian embryos.
极光激酶A（在人类中也被称为STK15/BTAK）是一种假定的癌蛋白，在许多人类癌症中自然过表达，它是保守的极光蛋白丝氨酸/苏氨酸激酶家族的成员，参与细胞周期G(2)-M期的调控。利用抗体显微注射、siRNA沉默和小分子抑制剂进行的体外研究表明，极光激酶A在有丝分裂的早期和晚期均发挥作用。然而，由于这些技术在特异性方面存在局限性，该激酶的确切功能作用仍有待明确阐明。为了确定其在体内的生理功能，我们构建了极光激酶A基因敲除的小鼠胚胎，这些胚胎在交配后3.5天（d.p.c.）的桑椹胚/囊胚阶段显示出严重缺陷，并在8.5 d.p.c.之前死亡。3.5 d.p.c.的基因敲除胚胎表现出生长迟缓，有丝分裂紊乱的细胞呈现纺锤体紊乱、染色体排列不齐和滞后以及出现微核细胞。这些发现为极光激酶A在正常有丝分裂纺锤体组装、染色体排列分离以及维持哺乳动物胚胎活力方面的重要生理作用提供了首个明确的遗传学证据。
