SUMO and cellular adaptive mechanisms

Abstract

The ubiquitin family member SUMO is a covalent regulator of proteins that functions in response to various stresses, and defects in SUMO-protein conjugation or deconjugation have been implicated in multiple diseases. The loss of the Ulp2 SUMO protease, which reverses SUMO-protein modifications, in the model eukaryote Saccharomyces cerevisiae is severely detrimental to cell fitness and has emerged as a useful model for studying how cells adapt to SUMO system dysfunction. Both short-term and long-term adaptive mechanisms are triggered depending on the length of time cells spend without this SUMO chain-cleaving enzyme. Such short-term adaptations include a highly specific multichromosome aneuploidy and large changes in ribosomal gene transcription. While aneuploid ulp2Δ cells survive, they suffer severe defects in growth and stress resistance. Over many generations, euploidy is restored, transcriptional programs are adjusted, and specific genetic changes that compensate for the loss of the SUMO protease are observed. These long-term adapted cells grow at normal rates with no detectable defects in stress resistance. In this review, we examine the connections between SUMO and cellular adaptive mechanisms more broadly.

Histone sumoylation and chromatin dynamics

“…Humans have nine known SUMO-specific proteases, while S. cerevisiae expresses two, Ulp1 and Ulp2 ( 8 ). Sumoylation of proteins is a critical regulator of many diverse cellular processes, including transcription, DNA replication, cell-cycle progression, mitochondrial dynamics, ribosome biogenesis, DNA repair, apoptosis and stress responses ( 9 , 10 ).…”

Advanced Technologies and Mechanisms for Yeast Evolutionary Engineering

“…Such responses can re-establish homeostasis and maintain viability by changes in metabolism, gene expression, cell-cycle progression, protein homeostasis, cytoskeletal organization, vesicular trafficking, and/or enzyme activity [32]. However, if a stress persists over time, cells often induce second-line adaptive mechanisms to promote genetic changes to maximize survival under continuous exposure [6]. These second-line adaptive responses need longer time to implement than the initial mechanisms.…”

“…These adaptations to re-establish homeostasis and maintain viability from the acute stress conditions appear changes in diverse cellular pathways [5]. When these responses are not sufficient to protect cells from stress, yeast activate second-line adaptive mechanisms that introduce genetic changes to confer resistance to the stress [6]. Biotechnology typically use this adaptive laboratory evolution to biosynthesize new desirable products, improve production yields, or reduce costs in industrial processes [7].…”

SUMOylation of Dorsal attenuates Toll/NF-κB signalling

“…2020). This increase in global SUMOylation, termed the SUMO-stress response, is an essential cyto-protective adaptation (Ryu et al . 2020).…”

“…SUMO regulates a plethora of cellular processes and is upregulated in response to protein-damaging stresses like heat shock, osmotic stress, proteasomal inhibition, immune stress, etc (Enserink 2015;Hegde et al 2020). This increase in global SUMOylation, termed the SUMO-stress response, is an essential cyto-protective adaptation (Ryu et al 2020).…”