Format

Send to

Choose Destination
Mol Biol Cell. 2017 Nov 7;28(23):3437-3446. doi: 10.1091/mbc.E17-06-0349. Epub 2017 Sep 20.

Cell-cycle transitions: a common role for stoichiometric inhibitors.

Author information

1
Department of Biochemistry, Oxford University, Oxford OX1 3QU, UK.
2
Department of Biological Sciences, Virginia Tech, Blacksburg, VA 24061.
3
Department of Biochemistry, Oxford University, Oxford OX1 3QU, UK bela.novak@bioch.ox.ac.uk.

Abstract

The cell division cycle is the process by which eukaryotic cells replicate their chromosomes and partition them to two daughter cells. To maintain the integrity of the genome, proliferating cells must be able to block progression through the division cycle at key transition points (called "checkpoints") if there have been problems in the replication of the chromosomes or their biorientation on the mitotic spindle. These checkpoints are governed by protein-interaction networks, composed of phase-specific cell-cycle activators and inhibitors. Examples include Cdk1:Clb5 and its inhibitor Sic1 at the G1/S checkpoint in budding yeast, APC:Cdc20 and its inhibitor MCC at the mitotic checkpoint, and PP2A:B55 and its inhibitor, alpha-endosulfine, at the mitotic-exit checkpoint. Each of these inhibitors is a substrate as well as a stoichiometric inhibitor of the cell-cycle activator. Because the production of each inhibitor is promoted by a regulatory protein that is itself inhibited by the cell-cycle activator, their interaction network presents a regulatory motif characteristic of a "feedback-amplified domineering substrate" (FADS). We describe how the FADS motif responds to signals in the manner of a bistable toggle switch, and then we discuss how this toggle switch accounts for the abrupt and irreversible nature of three specific cell-cycle checkpoints.

PMID:
28931595
PMCID:
PMC5687042
DOI:
10.1091/mbc.E17-06-0349
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center