Cyclin B1 is essential for mitosis in mouse embryos, and its nuclear export sets the time for mitosis.
Abstract
There is remarkable redundancy between the Cyclin-Cdk complexes that comprise the cell cycle machinery. None of the mammalian A-, D-, or E-type cyclins are required in development until implantation, and only Cdk1 is essential for early cell divisions. Cyclin B1 is essential for development, but whether it is required for cell division is contentious. Here, we used a novel imaging approach to analyze Cyclin B1-null embryos from fertilization onward. We show that Cyclin B1-/- embryos arrest in G2 phase after just two divisions. This is the earliest arrest of any Cyclin known and places Cyclin B1 with cdk1 as the essential regulators of the cell cycle. We reintroduced mutant proteins into this genetically null background to determine why Cyclin B1 is constantly exported from the nucleus. We found that Cyclin B1 must be exported from the nucleus for the cell to prevent premature entry to mitosis, and retaining Cyclin B1-Cdk1 at the plasma membrane precludes entry to mitosis.
Collections
Subject
Animals
Mice, Knockout
Mice
CDC2 Protein Kinase
Cell Cycle Proteins
DNA-Binding Proteins
Nuclear Proteins
Transcription Factors
Mitosis
Active Transport, Cell Nucleus
Phosphorylation
Embryonic Development
Protein-Tyrosine Kinases
cdc25 Phosphatases
Cyclin B1
Research team
Cell Division
Language
eng
Date accepted
2017-09-21
License start date
2018-01
Citation
The Journal of cell biology, 2018, 217 (1), pp. 179 - 193
Publisher
ROCKEFELLER UNIV PRESS
Except where otherwise noted, this item's license is described
as
https://creativecommons.org/licenses/by/4.0
Related items
Showing items related by title, author, creator and subject.
-
Phosphorylation-mediated interactions with TOPBP1 couple 53BP1 and 9-1-1 to control the G1 DNA damage checkpoint.
Bigot, N; Day, M; Baldock, RA; Watts, FZ; Oliver, AW; et al. (ELIFE SCIENCES PUBLICATIONS LTD, 2019-05-28)Coordination of the cellular response to DNA damage is organised by multi-domain 'scaffold' proteins, including 53BP1 and TOPBP1, which recognise post-translational modifications such as phosphorylation, methylation and ... -
Structural Basis for Auto-Inhibition of the NDR1 Kinase Domain by an Atypically Long Activation Segment.
Xiong, S; Lorenzen, K; Couzens, AL; Templeton, CM; Rajendran, D; et al. (CELL PRESS, 2018-08-07)The human NDR family kinases control diverse aspects of cell growth, and are regulated through phosphorylation and association with scaffolds such as MOB1. Here, we report the crystal structure of the human NDR1 kinase ... -
Multiparametric Analysis of Cell Shape Demonstrates that β-PIX Directly Couples YAP Activation to Extracellular Matrix Adhesion.
Sero, JE; Bakal, C (CELL PRESS, 2017-01-25)Mechanical signals from the extracellular matrix (ECM) and cellular geometry regulate the nuclear translocation of transcriptional regulators such as Yes-associated protein (YAP). Elucidating how physical signals control ...