Genetic interaction profiles of regulatory kinases differ between environmental conditions and cellular states.
Caloric Restriction
Cell Survival
/ genetics
Cyclin-Dependent Kinases
/ genetics
Epistasis, Genetic
Gene Deletion
Gene Expression Regulation, Fungal
/ genetics
Gene Ontology
Gene Regulatory Networks
Genetic Fitness
/ genetics
Genome-Wide Association Study
Genotype
Mutation
Phenotype
Phosphatidylinositol 3-Kinases
/ genetics
Protein Kinases
/ genetics
Saccharomyces cerevisiae
/ genetics
Saccharomyces cerevisiae Proteins
/ genetics
Signal Transduction
/ genetics
chronological aging
genetic interaction
nutrient starvation
quiescence
signaling kinase
Journal
Molecular systems biology
ISSN: 1744-4292
Titre abrégé: Mol Syst Biol
Pays: England
ID NLM: 101235389
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
14
08
2019
revised:
18
03
2020
accepted:
31
03
2020
entrez:
26
5
2020
pubmed:
26
5
2020
medline:
1
5
2021
Statut:
ppublish
Résumé
Cell growth and quiescence in eukaryotic cells is controlled by an evolutionarily conserved network of signaling pathways. Signal transduction networks operate to modulate a wide range of cellular processes and physiological properties when cells exit proliferative growth and initiate a quiescent state. How signaling networks function to respond to diverse signals that result in cell cycle exit and establishment of a quiescent state is poorly understood. Here, we studied the function of signaling pathways in quiescent cells using global genetic interaction mapping in the model eukaryotic cell, Saccharomyces cerevisiae (budding yeast). We performed pooled analysis of genotypes using molecular barcode sequencing (Bar-seq) to test the role of ~4,000 gene deletion mutants and ~12,000 pairwise interactions between all non-essential genes and the protein kinase genes TOR1, RIM15, and PHO85 in three different nutrient-restricted conditions in both proliferative and quiescent cells. We detect up to 10-fold more genetic interactions in quiescent cells than proliferative cells. We find that both individual gene effects and genetic interaction profiles vary depending on the specific pro-quiescence signal. The master regulator of quiescence, RIM15, shows distinct genetic interaction profiles in response to different starvation signals. However, vacuole-related functions show consistent genetic interactions with RIM15 in response to different starvation signals, suggesting that RIM15 integrates diverse signals to maintain protein homeostasis in quiescent cells. Our study expands genome-wide genetic interaction profiling to additional conditions, and phenotypes, and highlights the conditional dependence of epistasis.
Identifiants
pubmed: 32449603
doi: 10.15252/msb.20199167
pmc: PMC7247079
doi:
Substances chimiques
Saccharomyces cerevisiae Proteins
0
Protein Kinases
EC 2.7.-
Rim15 protein, S cerevisiae
EC 2.7.1.-
TOR1 protein, S cerevisiae
EC 2.7.1.137
Cyclin-Dependent Kinases
EC 2.7.11.22
PHO85 protein, S cerevisiae
EC 2.7.11.22
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e9167Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM107466
Pays : United States
Informations de copyright
© 2020 The Authors. Published under the terms of the CC BY 4.0 license.
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