Cell-cycle transitions: a common role for stoichiometric inhibitors

Simple item page
dc.contributor.authorHopkins, Michaelen
dc.contributor.authorTyson, John J.en
dc.contributor.authorNovak, Belaen
dc.contributor.departmentBiological Sciencesen
dc.date.accessioned2019-09-18T16:48:04Zen
dc.date.available2019-09-18T16:48:04Zen
dc.date.issued2017-11-07en
dc.description.abstractThe 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.en
dc.description.notesWe acknowledge financial support from EPSRC grant EP/G03706X/1 (to M.H.), the National Institutes of Health (USA) grant GM078989-10 (to J.J.T.), and BBSRC Strategic LoLa grant BB/M00354X/1 (to B.N.).en
dc.description.sponsorshipEPSRC [EP/G03706X/1]; National Institutes of Health (USA) [GM078989-10]; BBSRC Strategic LoLa grant [BB/M00354X/1]en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1091/mbc.E17-06-0349en
dc.identifier.eissn1939-4586en
dc.identifier.issn1059-1524en
dc.identifier.issue23en
dc.identifier.pmid28931595en
dc.identifier.urihttp://hdl.handle.net/10919/93755en
dc.identifier.volume28en
dc.language.isoenen
dc.rightsCreative Commons Attribution-NonCommercial-ShareAlike 3.0 Unporteden
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/en
dc.titleCell-cycle transitions: a common role for stoichiometric inhibitorsen
dc.title.serialMolecular Biology of the Cellen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
mbc.e17-06-0349.pdf
Size:
1.35 MB
Format:
Adobe Portable Document Format
Description:
Download

Collections

Scholarly Works, Biological Sciences