Shinde Swapnil R, Gangula Narmadha Reddy, Kavela Sridhar, Pandey Vimal, Maddika Subbareddy
Laboratory of Cell Death & Cell Survival, Centre for DNA Fingerprinting and Diagnostics (CDFD), Nampally, Hyderabad 500001, India.
Cell Signal. 2013 Dec;25(12):2511-7. doi: 10.1016/j.cellsig.2013.08.013. Epub 2013 Sep 3.
Mitotic progression is regulated by co-ordinated action of several proteins and is crucial for the maintenance of genomic stability. CHFR (Check point protein with FHA and RING domains) is an E3 ubiquitin ligase and a checkpoint protein that regulates entry into mitosis. But the molecular players involved in CHFR mediated mitotic checkpoint are not completely understood. In this study, we identified TOPK/PBK, a serine/threonine kinase and PTEN, a lipid phosphatase to play an important role in CHFR mediated mitotic transitions. We demonstrated that CHFR ubiquitinates and regulates TOPK levels, which is essential for its checkpoint function. Moreover, TOPK phosphorylates and inactivates PTEN, which in turn activates Akt that leads to proper G2/M progression. Collectively, our results reveal TOPK and PTEN as new players in CHFR mediated mitotic checkpoint.
有丝分裂进程受多种蛋白质的协同作用调控，对维持基因组稳定性至关重要。CHFR（含FHA和RING结构域的检查点蛋白）是一种E3泛素连接酶和检查点蛋白，可调节进入有丝分裂的过程。但是，参与CHFR介导的有丝分裂检查点的分子机制尚未完全明确。在本研究中，我们鉴定出丝氨酸/苏氨酸激酶TOPK/PBK和脂质磷酸酶PTEN在CHFR介导的有丝分裂转变中发挥重要作用。我们证明CHFR泛素化并调节TOPK水平，这对其检查点功能至关重要。此外，TOPK磷酸化并使PTEN失活，进而激活Akt，导致G2/M期正常进展。总体而言，我们的结果揭示了TOPK和PTEN是CHFR介导的有丝分裂检查点中的新参与者。
