Lee Sunyi, Jeong Ae Lee, Park Jeong Su, Han Sora, Jang Chang-Young, Kim Keun Il, Kim Yonghwan, Park Jong Hoon, Lim Jong-Seok, Lee Myung Sok, Yang Young
Division of Biological Sciences, Department of Life Systems, Research Center for Women's Disease, Sookmyung Women's University, Seoul, 140-742, Republic of Korea.
Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, Seoul, 140-742, Republic of Korea.
Cell Mol Life Sci. 2016 Sep;73(17):3375-86. doi: 10.1007/s00018-016-2162-9. Epub 2016 Feb 23.
Aurora B activation is triggered at the mitotic entry and required for proper microtubule-kinetochore attachment at mitotic phase. Therefore, Aurora B should be in inactive form in interphase to prevent aberrant cell cycle progression. However, it is unclear how the inactivation of Aurora B is sustained during interphase. In this study, we find that IK depletion-induced mitotic arrest leads to G2 arrest by Aurora B inhibition, indicating that IK depletion enhances Aurora B activation before mitotic entry. IK binds to Aurora B, and colocalizes on the nuclear foci during interphase. Our data further show that IK inhibits Aurora B activation through recruiting PP2A into IK and Aurora B complex. It is thus believed that IK, as a scaffold protein, guides PP2A into Aurora B to suppress its activity in interphase until mitotic entry.
Aurora B的激活在有丝分裂进入时被触发,并且在有丝分裂期对于正确的微管 - 动粒附着是必需的。因此,Aurora B在间期应处于无活性形式以防止异常的细胞周期进程。然而,尚不清楚Aurora B的失活在间期是如何维持的。在本研究中,我们发现IK缺失诱导的有丝分裂停滞通过抑制Aurora B导致G2期停滞,表明IK缺失在有丝分裂进入之前增强了Aurora B的激活。IK与Aurora B结合,并在间期共定位于核灶。我们的数据进一步表明,IK通过将PP2A招募到IK和Aurora B复合物中来抑制Aurora B的激活。因此,人们认为IK作为一种支架蛋白,引导PP2A作用于Aurora B,以在间期抑制其活性直至有丝分裂进入。