Molecular mechanisms creating bistable switches at cell cycle transitions

Autor: Anael Verdugo, P. K. Vinod, John J. Tyson, Bela Novak
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Zdroj: Open Biology, Vol 3, Iss 3 (2013)
Druh dokumentu: article
ISSN: 2046-2441
DOI: 10.1098/rsob.120179
Popis: Progression through the eukaryotic cell cycle is characterized by specific transitions, where cells move irreversibly from stage i−1 of the cycle into stage i. These irreversible cell cycle transitions are regulated by underlying bistable switches, which share some common features. An inhibitory protein stalls progression, and an activatory protein promotes progression. The inhibitor and activator are locked in a double-negative feedback loop, creating a one-way toggle switch that guarantees an irreversible commitment to move forward through the cell cycle, and it opposes regression from stage i to stage i−1. In many cases, the activator is an enzyme that modifies the inhibitor in multiple steps, whereas the hypo-modified inhibitor binds strongly to the activator and resists its enzymatic activity. These interactions are the basis of a reaction motif that provides a simple and generic account of many characteristic properties of cell cycle transitions. To demonstrate this assertion, we apply the motif in detail to the G1/S transition in budding yeast and to the mitotic checkpoint in mammalian cells. Variations of the motif might support irreversible cellular decision-making in other contexts.
Databáze: Directory of Open Access Journals