Osmolyte accumulation regulates the SUMOylation and inclusion dynamics of the prionogenic Cyc8-Tup1 transcription corepressor

Abstract

Environmental stressors can severely perturb cellular homeostasis and compromise viability. To cope with environmental stressors, eukaryotes have developed distinct signaling programs that allow for adaptation during different stress conditions. These programs often require a host of post-translational modifications that alter proteins to elicit appropriate cellular responses. One crucial protein modifier during stress is the small ubiquitin-like modifier SUMO. In many cases, however, the functions of stress dependent protein SUMOylation remain unclear. Previously, we showed that the conserved Saccharomyces cerevisiae Cyc8-Tup1 transcriptional corepressor complex undergoes transient hyperosmotic stress-induced SUMOylation and inclusion formation, which are important for appropriate regulation of hyperosmotic-stress genes. Here, we show the osmostress-responsive MAP kinase Hog1 regulates Cyc8 SUMOylation and inclusion formation via its role in the transcriptional activation of glycerol biosynthesis genes. Mutations that ablate Cyc8 SUMOylation can partially rescue the osmosensitivity of hog1Δ cells, and this is facilitated by inappropriate derepression of glycerol-biosynthesis genes. Furthermore, cells specifically unable to synthesize the osmolyte glycerol cause transient Cyc8 SUMOylation and inclusions to persist, indicating a regulatory role for glycerol to reestablish the basal state of Cyc8 following adaptation to hyperosmotic stress. These observations unveil a novel intersection between phosphorylation and SUMOylation networks, which are critical for shifting gene expression and metabolic programs during stress adaptation.

Complete, rapid and reversible regulation of the motility of a nano-biomolecular machine using an osmolyte trimethylamine-N-oxide

“…Therefore, such an ability to control activity of biomolecular motors at the molecular level as demonstrated in this work will greatly contribute to widen the applications of biomolecular motors in nanotechnology. At the same time, this work will motivate further exploration on the role of TMAO and other natural osmolytes in regulating the functions of biomolecular motors and other proteins in living organisms [40,[61][62].…”

Acute ethanol stress induces sumoylation of conserved chromatin structural proteins inSaccharomyces cerevisiae

“…From a transcriptional perspective, we know from our previous work ( Oeser et al. , 2016 ; Nadel et al. , 2019 ) and other studies ( Zhou et al.…”

“…We previously found that sumoylation modulates a transient phase separation in the Tup1-Cyc8 transcriptional co-repressor complex (Oeser et al, 2016), indicating a chromatin-modifying activity for sumoylation during hyperosmotic stress. From a transcriptional perspective, we know from our previous work (Nadel et al, 2019;Oeser et al, 2016) and other studies (Stielow et al, 2008;Zhao, 2018;Zhou et al, 2004) that genes involved either directly in transcription or its modulation have been reported to be sumoylated. How stress-induced sumoylation affects protein activity, localization, or stability remains an open question in the field, and it may be dictated by the magnitude and duration of the stress.…”

Not So Slim Anymore—Evidence for the Role of SUMO in the Regulation of Lipid Metabolism

“…This finding suggests that transcriptional regulation is another mechanism by which SUMO may control lipid metabolism in S. cerevisiae. The physiological significance of the regulation of lipid metabolism by SUMO is not entirely clear but the synthetic lethal phenotypes of erg8 or erg11 mutations in the background of deletions in two E3 ligases, siz1/2, suggest a functional link between SUMO and ergosterol synthesis [24,36,37]. The regulation of the synthesis of sterols and other products of the mevalonate pathway by SUMO in S. cerevisiae represents a mode of regulation conserved among other eukaryotes including C. elegans and mammals as will be discussed below.…”