Feedforward Regulation Ensures Stability and Rapid Reversibility of a Cellular State

Andreas Doncic, Jan M. Skotheim

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Cellular transitions are important for all life. Such transitions, including cell fate decisions, often employ positive feedback regulation to establish and stabilize new cellular states. However, positive feedback is unlikely to underlie stable cell-cycle arrest in yeast exposed to mating pheromone because the signaling pathway is linear, rather than bistable, over a broad range of extracellular pheromone concentration. We show that the stability of the pheromone-arrested state results from coherent feedforward regulation of the cell-cycle inhibitor Far1. This network motif is effectively isolated from the more complex regulatory network in which it is embedded. Fast regulation of Far1 by phosphorylation allows rapid cell-cycle arrest and reentry, whereas slow Far1 synthesis reinforces arrest. We expect coherent feedforward regulation to be frequently implemented at reversible cellular transitions because this network motif can achieve the ostensibly conflicting aims of arrest stability andrapid reversibility without loss of signaling information.

Original languageEnglish (US)
Pages (from-to)856-868
Number of pages13
JournalMolecular Cell
Volume50
Issue number6
DOIs
StatePublished - Jun 27 2013

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Pheromones
Cell Cycle Checkpoints
Cell Cycle
Yeasts
Phosphorylation

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Feedforward Regulation Ensures Stability and Rapid Reversibility of a Cellular State. / Doncic, Andreas; Skotheim, Jan M.

In: Molecular Cell, Vol. 50, No. 6, 27.06.2013, p. 856-868.

Research output: Contribution to journalArticle

Doncic, Andreas ; Skotheim, Jan M. / Feedforward Regulation Ensures Stability and Rapid Reversibility of a Cellular State. In: Molecular Cell. 2013 ; Vol. 50, No. 6. pp. 856-868.
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