Reimann J D, Freed E, Hsu J Y, Kramer E R, Peters J M, Jackson P K
Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA.
Cell. 2001 Jun 1;105(5):645-55. doi: 10.1016/s0092-8674(01)00361-0.
We have discovered an early mitotic inhibitor, Emi1, which regulates mitosis by inhibiting the anaphase promoting complex/cyclosome (APC). Emi1 is a conserved F box protein containing a zinc binding region essential for APC inhibition. Emi1 accumulates before mitosis and is ubiquitylated and destroyed in mitosis, independent of the APC. Emi1 immunodepletion from cycling Xenopus extracts strongly delays cyclin B accumulation and mitotic entry, whereas nondestructible Emi1 stabilizes APC substrates and causes a mitotic block. Emi1 binds the APC activator Cdc20, and Cdc20 can rescue an Emi1-induced block to cyclin B destruction. Our results suggest that Emi1 regulates progression through early mitosis by preventing premature APC activation, and may help explain the well-known delay between cyclin B/Cdc2 activation and cyclin B destruction.
我们发现了一种早期有丝分裂抑制剂Emi1,它通过抑制后期促进复合体/细胞周期体(APC)来调节有丝分裂。Emi1是一种保守的F盒蛋白,含有对APC抑制至关重要的锌结合区域。Emi1在有丝分裂前积累,并在有丝分裂过程中被泛素化和降解,这一过程不依赖于APC。从爪蟾卵母细胞提取物中免疫去除Emi1会强烈延迟细胞周期蛋白B的积累和有丝分裂的进入,而不可降解的Emi1会使APC底物稳定并导致有丝分裂阻滞。Emi1与APC激活因子Cdc20结合,并且Cdc20可以挽救Emi1诱导的细胞周期蛋白B降解阻滞。我们的结果表明,Emi1通过防止APC过早激活来调节早期有丝分裂进程,这可能有助于解释细胞周期蛋白B/Cdc2激活与细胞周期蛋白B降解之间众所周知的延迟现象。