Zhang Yue, Ni Jun, Huang Qiang, Ren Weihua, Yu Long, Zhao Shouyuan
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, China.
Biochem Biophys Res Commun. 2007 Jun 1;357(2):347-52. doi: 10.1016/j.bbrc.2007.03.129. Epub 2007 Mar 30.
Aurora-A is a centrosome-localized serine/threonine kinase that is overexpressed in multiple human cancers. Here, we report an intramolecular inhibitory regulation in Aurora-A between its N-terminal regulatory domain (aa 1-128, Nt) and the C-terminal catalytic domain (aa 129-403, Cd). Removal of Nt results in a significant increase in kinase activity. Nt inhibited the activity of the single C-terminal kinase domain, but had little effect on the activity of the full-length of Aurora-A. PP1 is not involved in this regulation, instead, Nt interacts Cd directly in vitro and in vivo. The non-Aurora box (aa 64-128) in the N-terminal negatively regulated the kinase activity of the C-terminal kinase domain by intramolecular interaction with aa 240-300 within the C-terminal.
极光激酶A是一种定位于中心体的丝氨酸/苏氨酸激酶，在多种人类癌症中过表达。在此，我们报道了极光激酶A在其N端调节结构域（第1至128位氨基酸，Nt）和C端催化结构域（第129至403位氨基酸，Cd）之间存在分子内抑制调节。去除Nt会导致激酶活性显著增加。Nt抑制单个C端激酶结构域的活性，但对全长极光激酶A的活性影响不大。蛋白磷酸酶1（PP1）不参与这种调节，相反，Nt在体外和体内都直接与Cd相互作用。N端的非极光框（第64至128位氨基酸）通过与C端内的第240至300位氨基酸进行分子内相互作用，对C端激酶结构域的激酶活性产生负调节作用。
