Exploiting the yeast stress-activated signaling network to inform on stress biology and disease signaling

Abstract

Healthy cells utilize intricate systems to monitor their environment and mount robust responses in the event of cellular stress. Whether stress arises from external insults or defects due to mutation and disease, cells must be able to respond precisely to mount the appropriate defenses. Multi-faceted stress responses are generally coupled with arrest of growth and cell-cycle progression, which both limits the transmission of damaged materials and serves to reallocate limited cellular resources toward defense. Therefore, stress defense versus rapid growth represent competing interests in the cell. How eukaryotic cells set the balance between defense versus proliferation, and in particular knowledge of the regulatory networks that control this decision, are poorly understood. In this perspective, we expand upon our recent work inferring the stress-activated signaling network in budding yeast, which captures pathways controlling stress defense and regulators of growth and cell-cycle progression. We highlight similarities between the yeast and mammalian stress responses and explore how stress-activated signaling networks in yeast can inform on signaling defects in human cancers.

Keywords: Growth control; Signal transduction; Stress response; Transcription.

Fig. 1

Proliferation and stress defense compete for limited resources in the cell. A simplified view of the signaling processes that occur in yeast and/or mammalian cells responding to growth-promoting signals versus cellular stress signals. Signaling molecules relevant in yeast are shown in blue and those unique to mammalian cells are shown in brown. See text for details