The Yeast GSK-3 Homologue Mck1 Is a Key Controller of Quiescence Entry and Chronological Lifespan

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The vast majority of eukaryotic cells exist in a non-proliferating state known as G0. However, how cells transit into, and survive during, the G0 state is poorly understood. Dysregulation of the G0 state leads to age-related diseases such as Alzheimer’s or cancers. We have revealed that the yeast Mck1 and Rim15 kinases, which function downstream of the PKA and/or TOR signaling pathways, coordinate cell cycle progression, cell size homeostasis, and the acquisition of a variety of G0-specific characteristics during the transition into stationary phase. Failure of this coordination compromises the ability of early stationary-phase cells to exit from quiescence and severely shortens their chronological lifespan. Further genetic analyses suggest that the nutrient sensor Ras2 may antagonize G0 entry via at least two pathways, one through the negative regulation of the G0-specific effectors (Mck1 and Rim15) and the other possibly involving its functions in promoting respiratory growth, a phenotype also intricately modulated by Mck1 and Rim15. As Ras2 and Rim15 have homolog in both insects and/or mammals, the identification of the GSK-3 homologue Mck1 and the characterisation of its relationship with Rim15 and Ras2 in G0 entry could provide important clues to the regulation of these processes in more complex organisms.

Vyšlo v časopise: The Yeast GSK-3 Homologue Mck1 Is a Key Controller of Quiescence Entry and Chronological Lifespan. PLoS Genet 11(6): e32767. doi:10.1371/journal.pgen.1005282
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005282

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