Interdisciplinary Graduate Program
Department of Biochemistry and Molecular Pharmacology
Cell Biology | Cellular and Molecular Physiology | Molecular Biology
In budding yeast, mating pheromones arrest the cell cycle in G1 phase via a pheromone-activated Cdk-inhibitor (CKI) protein, Far1. Alternate pathways must also exist, however, because deleting the cyclin CLN2 restores pheromone arrest to far1 cells. Here we probe whether these alternate pathways require the G1/S transcriptional repressors Whi5 and Stb1 or the CKI protein Sic1, whose metazoan analogues (Rb or p27) antagonize cell cycle entry. Removing Whi5 and Stb1 allows partial escape from G1 arrest in far1 cln2 cells, along with partial derepression of G1/S genes, which implies a repressor-independent route for inhibiting G1/S transcription. This route likely involves pheromone-induced degradation of Tec1, a transcriptional activator of the cyclin CLN1, because Tec1 stabilization also causes partial G1 escape in far1 cln2 cells, and this is additive with Whi5/Stb1 removal. Deleting SIC1 alone strongly disrupts Far1-independent G1 arrest, revealing that inhibition of B-type cyclin-Cdk activity can empower weak arrest pathways. Of interest, although far1 cln2 sic1 cells escaped G1 arrest, they lost viability during pheromone exposure, indicating that G1 exit is deleterious if the arrest signal remains active. Overall our findings illustrate how multiple distinct G1/S-braking mechanisms help to prevent premature cell cycle commitment and ensure a robust signal-induced G1 arrest.
Rights and Permissions
Copyright 2013 Pope and Pryciak. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).
DOI of Published Version
Pope PA, Pryciak PM. Functional overlap among distinct G1/S inhibitory pathways allows robust G1 arrest by yeast mating pheromones. Mol Biol Cell. 2013 Dec;24(23):3675-88. doi: 10.1091/mbc.E13-07-0373. Link to article on publisher's site
Molecular biology of the cell
Pope PA, Pryciak PM. (2013). Functional overlap among distinct G1/S inhibitory pathways allows robust G1 arrest by yeast mating pheromones. Morningside Graduate School of Biomedical Sciences Student Publications. https://doi.org/10.1091/mbc.E13-07-0373. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/1844