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周期蛋白 B3 是一种快速作用的主要周期蛋白,可驱动早期胚胎的快速有丝分裂。

Cyclin B3 is a dominant fast-acting cyclin that drives rapid early embryonic mitoses.

机构信息

Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, USA.

Ludwig Institute for Cancer Research , La Jolla, CA, USA.

出版信息

J Cell Biol. 2024 Nov 4;223(11). doi: 10.1083/jcb.202308034. Epub 2024 Aug 6.

Abstract

Mitosis in early embryos often proceeds at a rapid pace, but how this pace is achieved is not understood. Here, we show that cyclin B3 is the dominant driver of rapid embryonic mitoses in the C. elegans embryo. Cyclins B1 and B2 support slow mitosis (NEBD to anaphase ∼600 s), but the presence of cyclin B3 dominantly drives the approximately threefold faster mitosis observed in wildtype. Multiple mitotic events are slowed down in cyclin B1 and B2-driven mitosis, and cyclin B3-associated Cdk1 H1 kinase activity is ∼25-fold more active than cyclin B1-associated Cdk1. Addition of cyclin B1 to fast cyclin B3-only mitosis introduces an ∼60-s delay between completion of chromosome alignment and anaphase onset; this delay, which is important for segregation fidelity, is dependent on inhibitory phosphorylation of the anaphase activator Cdc20. Thus, cyclin B3 dominance, coupled to a cyclin B1-dependent delay that acts via Cdc20 phosphorylation, sets the rapid pace and ensures mitotic fidelity in the early C. elegans embryo.

摘要

早期胚胎中的有丝分裂通常进行得很快,但人们并不了解这种速度是如何实现的。在这里,我们表明,在秀丽隐杆线虫胚胎中,周期蛋白 B3 是快速有丝分裂的主要驱动因素。周期蛋白 B1 和 B2 支持缓慢的有丝分裂(从核膜破裂到后期约 600 秒),但周期蛋白 B3 的存在主要驱动了在野生型中观察到的大约三倍的更快的有丝分裂。在周期蛋白 B1 和 B2 驱动的有丝分裂中,多个有丝分裂事件会减慢,并且与周期蛋白 B1 相关的 Cdk1 H1 激酶活性比与周期蛋白 B3 相关的 Cdk1 高约 25 倍。将周期蛋白 B1 添加到快速的仅周期蛋白 B3 有丝分裂中,会在染色体对齐完成和后期开始之间引入约 60 秒的延迟;这种延迟对于分离保真度很重要,并且依赖于后期激活物 Cdc20 的抑制性磷酸化。因此,周期蛋白 B3 的主导地位,加上通过 Cdc20 磷酸化作用的周期蛋白 B1 依赖性延迟,设定了早期秀丽隐杆线虫胚胎的快速节奏,并确保了有丝分裂的保真度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d29/11303871/80af02c40256/JCB_202308034_FigS1.jpg

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