title: The Rts1 regulatory subunit of protein phosphatase 2A is required for control of G1 cyclin transcription and nutrient modulation of cell size.
abstract: The key molecular event that marks entry into the cell cycle is transcription of G1 cyclins, which bind and activate cyclin-dependent kinases. In yeast cells, initiation of G1 cyclin transcription is linked to achievement of a critical cell size, which contributes to cell-size homeostasis. The critical cell size is modulated by nutrients, such that cells growing in poor nutrients are smaller than cells growing in rich nutrients. Nutrient modulation of cell size does not work through known critical regulators of G1 cyclin transcription and is therefore thought to work through a distinct pathway. Here, we report that Rts1, a highly conserved regulatory subunit of protein phosphatase 2A (PP2A), is required for normal control of G1 cyclin transcription. Loss of Rts1 caused delayed initiation of bud growth and delayed and reduced accumulation of G1 cyclins. Expression of the G1 cyclin CLN2 from an inducible promoter rescued the delayed bud growth in rts1Delta cells, indicating that Rts1 acts at the level of transcription. Moreover, loss of Rts1 caused altered regulation of Swi6, a key component of the SBF transcription factor that controls G1 cyclin transcription. Epistasis analysis revealed that Rts1 does not work solely through several known critical upstream regulators of G1 cyclin transcription. Cells lacking Rts1 failed to undergo nutrient modulation of cell size. Together, these observations demonstrate that Rts1 is a key player in pathways that link nutrient availability, cell size, and G1 cyclin transcription. Since Rts1 is highly conserved, it may function in similar pathways in vertebrates.
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California Santa Cruz, Santa Cruz, California, United States of America.
authors.forename: Karen
authors.initials: K
authors.lastname: Artiles
authors.forename: Stephanie
authors.initials: S
authors.lastname: Anastasia
authors.forename: Derek
authors.initials: D
authors.lastname: McCusker
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Kellogg
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D019295:Computational Biology / Q000379:methods*; D056766:Cyclin G1 / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D016193:G1 Phase; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015003:Yeasts / Q000235:genetics / Q000254:growth & development
chemical_list: D018797:Cell Cycle Proteins; D056766:Cyclin G1; D003598:Cytoskeletal Proteins; D005656:Fungal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D021122:Protein Subunits; D012097:Repressor Proteins; D014157:Transcription Factors; D054648:Protein Phosphatase 2