Center for Reproductive Sciences & School of Biomedical Sciences, University of Newcastle, Callaghan, New South Wales, Australia.
Curr Top Dev Biol. 2013;102:207-26. doi: 10.1016/B978-0-12-416024-8.00007-6.
Mammalian oocytes spend the majority of their lives in a dormant state, residing in primordial follicles. This arrest, most analogous to the G2 stage of the mitotic cell cycle division, is only broken in the hours preceding ovulation, when a hormonal rise induces meiotic resumption and entry into the first meiotic division. At a molecular level, this event is triggered by CDK1 activity, and here, we examine how CDK1 is suppressed during meiotic arrest and raised for oocyte maturation. We focus on signaling: intercellular signaling between the oocyte and the somatic cells of the follicle, and spatial signaling involving the anaphase-promoting complex (APC) within the oocyte. Meiotic arrest is achieved through APC(FZR1)-mediated cyclin B1 degradation. Once meiotic resumption resumes, CDK1 levels rise, but its activity eventually needs to be suppressed for completion of the first meiotic division. This is achieved by APC(CDC20), whose activity is critically regulated by the spindle assembly checkpoint, and which induces both a loss in CDK1 activity as well as the cohesive ties holding chromosomes together.
哺乳动物卵母细胞在其大部分生命中处于休眠状态,存在于原始卵泡中。这种停滞最类似于有丝分裂细胞周期分裂的 G2 期,仅在排卵前数小时被打破,此时激素上升诱导减数分裂恢复并进入第一次减数分裂。在分子水平上,这一事件由 CDK1 活性触发,在这里,我们研究 CDK1 在减数分裂停滞期间如何受到抑制,并在卵母细胞成熟时升高。我们专注于信号转导:卵母细胞和卵泡体细胞之间的细胞间信号转导,以及卵母细胞内涉及后期促进复合物 (APC) 的空间信号转导。减数分裂停滞是通过 APC(FZR1)介导的细胞周期蛋白 B1 降解来实现的。一旦减数分裂恢复,CDK1 水平上升,但为了完成第一次减数分裂,其活性最终需要受到抑制。这是通过 APC(CDC20)实现的,其活性受到纺锤体组装检查点的严格调控,这不仅导致 CDK1 活性丧失,还导致保持染色体结合的粘着连接丧失。